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Paolo M. Suter - One of the best experts on this subject based on the ideXlab platform.
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metabolic effects of i v Propacetamol metamizol or external cooling in critically ill febrile sedated patients
BJA: British Journal of Anaesthesia, 1997Co-Authors: Barbara Poblete, P. König, Jacques-a Romand, Claude Pichard, Paolo M. SuterAbstract:We have measured the metabolic response to sequential administration of Propacetamol, metamizol and/or external cooling in 20 febrile patients under sedation and analgesia and during mechanical ventilation. There was no change in temperature (T degree) after Propacetamol therapy, whereas after metamizol only a small decrease was noted (from 38.9 (SEM 0.2) to 38.5 (0.3) degrees C; P = 0.02). External cooling produced a significant decrease in T degree (39.1 (0.2) to 37.1 (0.2) degrees C; P
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Metabolic effects of i.v. Propacetamol, metamizol or external cooling in critically ill febrile sedated patients
British Journal of Anaesthesia, 1997Co-Authors: Barbara Poblete, P. König, Jacques-a Romand, Claude Pichard, Paolo M. SuterAbstract:We have measured the metabolic response to sequential administration of Propacetamol, metamizol and/or external cooling in 20 febrile patients under sedation and analgesia and during mechanical ventilation. There was no change in temperature (T degree) after Propacetamol therapy, whereas after metamizol only a small decrease was noted (from 38.9 (SEM 0.2) to 38.5 (0.3) degrees C; P = 0.02). External cooling produced a significant decrease in T degree (39.1 (0.2) to 37.1 (0.2) degrees C; P < 0.0001) accompanied by a decrease in energy expenditure (EE) (2034 (73) to 1791 (88) kcal day-1; P < 0.004). Heart rate and minute ventilation decreased significantly in parallel. There were no other changes in haemodynamics or pulmonary gas exchanges. We conclude that Propacetamol and metamizol did not produce a clinically significant decrease in T degree in febrile ICU patients whereas external cooling decreased both T degree and EE. The parallel decrease in body temperature and EE seemed to be related to opioid administration or sedation, or both.
Roman Schumann - One of the best experts on this subject based on the ideXlab platform.
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single dose intravenous paracetamol or intravenous Propacetamol for postoperative pain
Cochrane Database of Systematic Reviews, 2016Co-Authors: Ewan D Mcnicol, Mckenzie C Ferguson, Simon Haroutounian, Daniel B Carr, Roman SchumannAbstract:Background This is an updated version of the original Cochrane review published in Issue 10, 2011. Paracetamol (acetaminophen) is the most commonly prescribed analgesic for the treatment of acute pain. It may be administered orally, rectally, or intravenously. The efficacy and safety of intravenous (IV) formulations of paracetamol, IV paracetamol, and IV Propacetamol (a prodrug that is metabolized to paracetamol), compared with placebo and other analgesics, is unclear. Objectives To assess the efficacy and safety of IV formulations of paracetamol for the treatment of postoperative pain in both adults and children. Search methods We ran the search for the previous review in May 2010. For this update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 1), MEDLINE (May 2010 to 16 February 2016), EMBASE (May 2010 to 16 February 2016), LILACS (2010 to 2016), a clinical trials registry, and reference lists of reviews for randomized controlled trials (RCTs) in any language and we retrieved articles. Selection criteria Randomized, double-blind, placebo- or active-controlled single dose clinical trials of IV paracetamol or IV Propacetamol for acute postoperative pain in adults or children. Data collection and analysis Two review authors independently extracted data, which included demographic variables, type of surgery, interventions, efficacy, and adverse events. We contacted study authors for additional information. We graded each included study for methodological quality by assessing risk of bias and employed the GRADE approach to assess the overall quality of the evidence. Main results We included 75 studies (36 from the original review and 39 from our updated review) enrolling a total of 7200 participants. Among primary outcomes, 36% of participants receiving IV paracetamol/Propacetamol experienced at least 50% pain relief over four hours compared with 16% of those receiving placebo (number needed to treat to benefit (NNT) = 5; 95% confidence interval (CI) 3.7 to 5.6, high quality evidence). The proportion of participants in IV paracetamol/Propacetamol groups experiencing at least 50% pain relief diminished over six hours, as reflected in a higher NNT of 6 (4.6 to 7.1, moderate quality evidence). Mean pain intensity at four hours was similar when comparing IV paracetamol and placebo, but was seven points lower on a 0 to 100 visual analog scale (0 = no pain, 100 = worst pain imaginable, 95% CI -9 to -6, low quality evidence) in those receiving paracetamol at six hours. For secondary outcomes, participants receiving IV paracetamol/Propacetamol required 26% less opioid over four hours and 16% less over six hours (moderate quality evidence) than those receiving placebo. However, this did not translate to a clinically meaningful reduction in opioid-induced adverse events. Meta-analysis of efficacy comparisons between IV paracetamol/Propacetamol and active comparators (e.g., opioids or nonsteroidal anti-inflammatory drugs) were either not statistically significant, not clinically significant, or both. Adverse events occurred at similar rates with IV paracetamol or IV Propacetamol and placebo. However, pain on infusion occurred more frequently in those receiving IV Propacetamol versus placebo (23% versus 1%). Meta-analysis did not demonstrate clinically meaningful differences between IV paracetamol/Propacetamol and active comparators for any adverse event. Authors' conclusions Since the last version of this review, we have found 39 new studies providing additional information. Most included studies evaluated adults only. We reanalyzed the data but the results did not substantially alter any of our previously published conclusions. This review provides high quality evidence that a single dose of either IV paracetamol or IV Propacetamol provides around four hours of effective analgesia for about 36% of patients with acute postoperative pain. Low to very low quality evidence demonstrates that both formulations are associated with few adverse events, although patients receiving IV Propacetamol have a higher incidence of pain on infusion than both placebo and IV paracetamol.
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The Cochrane Library - Single dose intravenous paracetamol or intravenous Propacetamol for postoperative pain.
Cochrane Database of Systematic Reviews, 2016Co-Authors: Ewan D Mcnicol, Mckenzie C Ferguson, Simon Haroutounian, Daniel B Carr, Roman SchumannAbstract:Background This is an updated version of the original Cochrane review published in Issue 10, 2011. Paracetamol (acetaminophen) is the most commonly prescribed analgesic for the treatment of acute pain. It may be administered orally, rectally, or intravenously. The efficacy and safety of intravenous (IV) formulations of paracetamol, IV paracetamol, and IV Propacetamol (a prodrug that is metabolized to paracetamol), compared with placebo and other analgesics, is unclear. Objectives To assess the efficacy and safety of IV formulations of paracetamol for the treatment of postoperative pain in both adults and children. Search methods We ran the search for the previous review in May 2010. For this update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 1), MEDLINE (May 2010 to 16 February 2016), EMBASE (May 2010 to 16 February 2016), LILACS (2010 to 2016), a clinical trials registry, and reference lists of reviews for randomized controlled trials (RCTs) in any language and we retrieved articles. Selection criteria Randomized, double-blind, placebo- or active-controlled single dose clinical trials of IV paracetamol or IV Propacetamol for acute postoperative pain in adults or children. Data collection and analysis Two review authors independently extracted data, which included demographic variables, type of surgery, interventions, efficacy, and adverse events. We contacted study authors for additional information. We graded each included study for methodological quality by assessing risk of bias and employed the GRADE approach to assess the overall quality of the evidence. Main results We included 75 studies (36 from the original review and 39 from our updated review) enrolling a total of 7200 participants. Among primary outcomes, 36% of participants receiving IV paracetamol/Propacetamol experienced at least 50% pain relief over four hours compared with 16% of those receiving placebo (number needed to treat to benefit (NNT) = 5; 95% confidence interval (CI) 3.7 to 5.6, high quality evidence). The proportion of participants in IV paracetamol/Propacetamol groups experiencing at least 50% pain relief diminished over six hours, as reflected in a higher NNT of 6 (4.6 to 7.1, moderate quality evidence). Mean pain intensity at four hours was similar when comparing IV paracetamol and placebo, but was seven points lower on a 0 to 100 visual analog scale (0 = no pain, 100 = worst pain imaginable, 95% CI -9 to -6, low quality evidence) in those receiving paracetamol at six hours. For secondary outcomes, participants receiving IV paracetamol/Propacetamol required 26% less opioid over four hours and 16% less over six hours (moderate quality evidence) than those receiving placebo. However, this did not translate to a clinically meaningful reduction in opioid-induced adverse events. Meta-analysis of efficacy comparisons between IV paracetamol/Propacetamol and active comparators (e.g., opioids or nonsteroidal anti-inflammatory drugs) were either not statistically significant, not clinically significant, or both. Adverse events occurred at similar rates with IV paracetamol or IV Propacetamol and placebo. However, pain on infusion occurred more frequently in those receiving IV Propacetamol versus placebo (23% versus 1%). Meta-analysis did not demonstrate clinically meaningful differences between IV paracetamol/Propacetamol and active comparators for any adverse event. Authors' conclusions Since the last version of this review, we have found 39 new studies providing additional information. Most included studies evaluated adults only. We reanalyzed the data but the results did not substantially alter any of our previously published conclusions. This review provides high quality evidence that a single dose of either IV paracetamol or IV Propacetamol provides around four hours of effective analgesia for about 36% of patients with acute postoperative pain. Low to very low quality evidence demonstrates that both formulations are associated with few adverse events, although patients receiving IV Propacetamol have a higher incidence of pain on infusion than both placebo and IV paracetamol.
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The Cochrane Library - Single dose intravenous Propacetamol or intravenous paracetamol for postoperative pain
Cochrane Database of Systematic Reviews, 2011Co-Authors: Aikaterini Tzortzopoulou, Ewan D Mcnicol, M S Cepeda, Marie Belle D Francia, Tamman Farhat, Roman SchumannAbstract:Background Paracetamol (acetaminophen) is the most commonly prescribed analgesic for the treatment of acute pain. It may be administered orally or intravenously. The efficacy and safety of intravenous (IV) formulations of paracetamol, IV paracetamol and IV Propacetamol, compared with placebo and other analgesics, is unclear. Objectives To assess the efficacy and safety of IV formulations of paracetamol for treatment of postoperative pain in both adults and children. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 2), MEDLINE (1950 to May 2010), EMBASE (1980 to 2010, Week 18), LILACS (1992 to May 2010) and reference lists of retrieved articles. Selection criteria Randomized, double-blind, placebo- or active-controlled single dose clinical trials of IV Propacetamol or IV paracetamol for acute postoperative pain in adults or children. Data collection and analysis Two review authors independently assessed the risk of bias and extracted data. We contacted study authors for additional information. We collected adverse event information from the studies. Main results Thirty-six studies (3896 participants) were included. Thirty-seven percent of participants receiving IV Propacetamol/paracetamol experienced at least 50% pain relief over four hours compared with 16% of those receiving placebo (number needed to treat to benefit (NNT = 4.0; 95% confidence interval 3.5 to 4.8). The proportion of participants in IV Propacetamol/paracetamol groups experiencing at least 50% pain relief diminished over six hours, as reflected in a higher NNT of 5.3 (4.2 to 6.7). Participants receiving IV Propacetamol/paracetamol required 30% less opioid over four hours than those receiving placebo. However, this did not translate to a reduction in opioid-induced adverse events. Meta-analysis of efficacy comparisons between IV Propacetamol/paracetamol and active comparators (opioids or nonsteroidal anti-inflammatories (NSAIDs)) were either not statistically significant, not clinically significant, or both. Adverse events occurred at similar rates with IV Propacetamol or IV paracetamol and placebo. However, pain on infusion occurred more frequently in those receiving IV Propacetamol versus placebo (23% versus 1%). Meta-analysis did not demonstrate statistically significant differences between IV Propacetamol/paracetamol and active comparators for any adverse event except a reduction in the rate of hypotension versus NSAIDs and a reduction in the rate of gastrointestinal disorders versus opioids. Authors' conclusions A single dose of both IV Propacetamol and IV paracetamol provides around four hours of effective analgesia for about 37% of patients with acute postoperative pain. Both formulations are associated with few adverse events, although patients receiving IV Propacetamol have a higher incidence of pain on infusion than both placebo and IV paracetamol.
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single dose intravenous Propacetamol or intravenous paracetamol for postoperative pain
Cochrane Database of Systematic Reviews, 2011Co-Authors: Aikaterini Tzortzopoulou, Ewan D Mcnicol, Marie Belle D Francia, Tamman Farhat, Soledad M Cepeda, Roman SchumannAbstract:Background Paracetamol (acetaminophen) is the most commonly prescribed analgesic for the treatment of acute pain. It may be administered orally or intravenously. The efficacy and safety of intravenous (IV) formulations of paracetamol, IV paracetamol and IV Propacetamol, compared with placebo and other analgesics, is unclear. Objectives To assess the efficacy and safety of IV formulations of paracetamol for treatment of postoperative pain in both adults and children. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 2), MEDLINE (1950 to May 2010), EMBASE (1980 to 2010, Week 18), LILACS (1992 to May 2010) and reference lists of retrieved articles. Selection criteria Randomized, double-blind, placebo- or active-controlled single dose clinical trials of IV Propacetamol or IV paracetamol for acute postoperative pain in adults or children. Data collection and analysis Two review authors independently assessed the risk of bias and extracted data. We contacted study authors for additional information. We collected adverse event information from the studies. Main results Thirty-six studies (3896 participants) were included. Thirty-seven percent of participants receiving IV Propacetamol/paracetamol experienced at least 50% pain relief over four hours compared with 16% of those receiving placebo (number needed to treat to benefit (NNT = 4.0; 95% confidence interval 3.5 to 4.8). The proportion of participants in IV Propacetamol/paracetamol groups experiencing at least 50% pain relief diminished over six hours, as reflected in a higher NNT of 5.3 (4.2 to 6.7). Participants receiving IV Propacetamol/paracetamol required 30% less opioid over four hours than those receiving placebo. However, this did not translate to a reduction in opioid-induced adverse events. Meta-analysis of efficacy comparisons between IV Propacetamol/paracetamol and active comparators (opioids or nonsteroidal anti-inflammatories (NSAIDs)) were either not statistically significant, not clinically significant, or both. Adverse events occurred at similar rates with IV Propacetamol or IV paracetamol and placebo. However, pain on infusion occurred more frequently in those receiving IV Propacetamol versus placebo (23% versus 1%). Meta-analysis did not demonstrate statistically significant differences between IV Propacetamol/paracetamol and active comparators for any adverse event except a reduction in the rate of hypotension versus NSAIDs and a reduction in the rate of gastrointestinal disorders versus opioids. Authors' conclusions A single dose of both IV Propacetamol and IV paracetamol provides around four hours of effective analgesia for about 37% of patients with acute postoperative pain. Both formulations are associated with few adverse events, although patients receiving IV Propacetamol have a higher incidence of pain on infusion than both placebo and IV paracetamol.
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single dose intravenous paracetamol or Propacetamol for prevention or treatment of postoperative pain a systematic review and meta analysis
BJA: British Journal of Anaesthesia, 2011Co-Authors: Ewan D Mcnicol, Aikaterini Tzortzopoulou, M S Cepeda, Marie Belle D Francia, Tamman Farhat, Roman SchumannAbstract:Summary. Paracetamol is the most commonly prescribed analgesic for the treatment of acute pain. The efficacy and safety of i.v. formulations of paracetamol is unclear. We performed a systematic search (multiple databases, bibliographies, any language, to May 2010) for single-dose, randomized, controlled clinical trials of Propacetamol or i.v. paracetamol for acute postoperative pain in adults or children. Thirty-six studies involving 3896 patients were included. For the primary outcome, 37% of patients (240/367) receiving Propacetamol or i.v. paracetamol experienced at least 50% pain relief over 4 h compared with 16% (68/527) receiving placebo (number needed to treat¼4.0; 95% confidence interval, 3.5–4.8). The proportion of patients in Propacetamol or i.v. paracetamol groups experiencing at least 50% pain relief diminished over 6 h. Patients receiving Propacetamol or paracetamol required 30% less opioid over 4 h and 16% less opioid over 6 h than those receiving placebo. However, this did not translate to a reduction in opioid-induced adverse events (AEs). Similar comparisons between Propacetamol or i.v. paracetamol and active comparators were either not statistically significant, not clinically significant, or both. AEs occurred at similar rates with Propacetamol or i.v. paracetamol and placebo. However, pain on infusion occurred more frequently in those receiving Propacetamol compared with placebo (23% vs 1%). A single dose of either Propacetamol or i.v. paracetamol provides around 4 h of effective analgesia for about 37% of patients with acute postoperative pain. Both formulations are associated with few AEs, although patients receiving Propacetamol have a higher incidence of pain on infusion.
リンツ クラウス - One of the best experts on this subject based on the ideXlab platform.
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1r 4r 6 fluoro n n dimethyl 4 phenyl 4 9 dihydro 3 h spiro cyclohexane 1 1 pyrano 3 4 b indol 4 amine and pharmaceutical compositions comprising paracetamol or Propacetamol
2013Co-Authors: フロシュ シュテファニー, リンツ クラウスAbstract:The present invention, (1r, 4r)-6'-fluoro -N, N-dimethyl-4-phenyl-4 ', 9'-dihydro -3'H--spiro [cyclohexane-1,1'-pyrano [3, 4, b] indol] -4-amine and a first pharmacologically active ingredient selected from the physiologically acceptable salts thereof, medicaments containing a second pharmacologically active ingredient selected from paracetamol and Propacetamol It relates to a composition.
Dick Tibboel - One of the best experts on this subject based on the ideXlab platform.
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Pharmacokinetics of single dose intravenous Propacetamol in neonates: effect of gestational age.
Archives of disease in childhood. Fetal and neonatal edition, 2020Co-Authors: Karel Allegaert, C D Van Der Marel, Anne Debeer, Mal Pluim, R A Van Lingen, Christine Vanhole, Dick Tibboel, Hugo DevliegerAbstract:To investigate the pharmacokinetics and pharmacodynamics of single dose Propacetamol in preterm and term infants on the first day of life. Neonates were stratified by gestational age. Preterm (< 37 weeks) and term (37-41 weeks) infants received a single dose of Propacetamol in the first 24 hours of life when they had minor, painful procedures or as additional treatment in infants receiving opioids. Blood samples were taken from an arterial line, and pain was evaluated by a multidimensional pain scale. Results were reported as mean (SD). Student's t and Wilcoxon tests were used to compare the groups. Thirty neonates were included, 10 of which were term infants. Serum half life was 277 (143) minutes in the preterm infants and 172 (59) minutes in the term infants (p < 0.05). Clearance was 0.116 (0.08) litre/kg/h in the preterm infants and 0.170 (0.06) litre/kg/h in the term infants (p < 0.05). Gestational age correlated with serum half life (r = -0.46). No effect of sex or administration of prenatal steroids was found on the pharmacokinetics of paracetamol. In neonates who only received Propacetamol (n = 15), the level of analgesia seemed to be associated with the therapeutic (> 5 mg/l) level. A correlation was found between gestational age and the serum half life of Propacetamol. The maturational trend of clearance and half life in preterm and term neonates is in line with data on the pharmacokinetics of Propacetamol beyond the newborn period.
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pharmacokinetics and analgesic effects of intravenous Propacetamol vs rectal paracetamol in children after major craniofacial surgery
Pediatric Anesthesia, 2008Co-Authors: Sandra Prins, Dick Tibboel, Brian J Anderson, Monique Van Dijk, Pim Van Leeuwen, Susan Searle, Ron A A MathotAbstract:Background: The pharmacokinetics and analgesic effects of intravenous and rectal paracetamol were compared in nonventilated infants after craniofacial surgery in a double-blind placebo controlled study. Methods: During surgery all infants (6 months-2 years) received a rectal loading dose of 40 mg.kg(-1) paracetamol 2 h before anticipated extubation. On admittance to the pediatric surgical ICU, the children were randomized to receive either a 15 min intravenous infusion of 40 mg.kg(-1) Propacetamol, a prodrug of paracetamol, or 20 mg.kg(-1) paracetamol rectally every 6 h. A population pharmacokinetic analysis of the paracetamol plasma concentration time-profiles was undertaken using nonlinear mixed effects models. The visual analogue scale (VAS) (score 0-10 cm) and COMFORT Behavior scale (score 6-30) were used to monitor analgesia in the 24-h period following surgery. Results: Twelve infants received intravenous Propacetamol and 14 paracetamol suppositories. Paracetamol pharmacokinetics were described according to a two-compartmental model with linear disposition. Pharmacokinetic parameters were standardized to a 70 kg person using allometric '1/4 power' models. Parameter estimates were: absorption half-life from the rectum 4.6 h, Propacetamol hydrolysis half-life 0.028 h, clearance 12 l.h(-1).70 kg(-1), intercompartmental clearance 116 l.h(-1).70 kg(-1), central and peripheral volume of distribution 7.9 and 44 l.70 kg(-1), respectively. During the 24-h study period 22 infants exhibited VAS scores = 4 cm. Nine patients in the rectal treatment group and three patients in the intravenous treatment group received midazolam for COMFORT-B scores exceeding 17 (P <0.05). Conclusions: Intravenous Propacetamol proved to be more effective than rectal paracetamol in infants after craniofacial surgery. Midazolam was more frequently administered to patients receiving paracetamol suppositories, indicating that these children experienced more distress, possibly caused by pain.
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Pharmacokinetics and analgesic effects of intravenous Propacetamol vs rectal paracetamol in children after major craniofacial surgery
Pediatric Anesthesia, 2008Co-Authors: Sandra A. Prins, Dick Tibboel, Brian J Anderson, Monique Van Dijk, Pim Van Leeuwen, Susan Searle, Ron A A MathotAbstract:Background: The pharmacokinetics and analgesic effects of intravenous and rectal paracetamol were compared in nonventilated infants after craniofacial surgery in a double-blind placebo controlled study. Methods: During surgery all infants (6 months-2 years) received a rectal loading dose of 40 mg.kg(-1) paracetamol 2 h before anticipated extubation. On admittance to the pediatric surgical ICU, the children were randomized to receive either a 15 min intravenous infusion of 40 mg.kg(-1) Propacetamol, a prodrug of paracetamol, or 20 mg.kg(-1) paracetamol rectally every 6 h. A population pharmacokinetic analysis of the paracetamol plasma concentration time-profiles was undertaken using nonlinear mixed effects models. The visual analogue scale (VAS) (score 0-10 cm) and COMFORT Behavior scale (score 6-30) were used to monitor analgesia in the 24-h period following surgery. Results: Twelve infants received intravenous Propacetamol and 14 paracetamol suppositories. Paracetamol pharmacokinetics were described according to a two-compartmental model with linear disposition. Pharmacokinetic parameters were standardized to a 70 kg person using allometric '1/4 power' models. Parameter estimates were: absorption half-life from the rectum 4.6 h, Propacetamol hydrolysis half-life 0.028 h, clearance 12 l.h(-1).70 kg(-1), intercompartmental clearance 116 l.h(-1).70 kg(-1), central and peripheral volume of distribution 7.9 and 44 l.70 kg(-1), respectively. During the 24-h study period 22 infants exhibited VAS scores = 4 cm. Nine patients in the rectal treatment group and three patients in the intravenous treatment group received midazolam for COMFORT-B scores exceeding 17 (P
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Intra‐ and interindividual variability of glucuronidation of paracetamol during repeated administration of Propacetamol in neonates
Acta Paediatrica, 2007Co-Authors: Karel Allegaert, Christine Vanhole, Hugo Devlieger, Rene Verbesselt, J De Hoon, Dick TibboelAbstract:Background: Major changes in drug clearance and metabolism are observed during infancy, in part based on ontogenic regulation of various metabolic pathways. Since paracetamol provides a good substrate to study UGT (1A6) activity, urinary metabolites of Propacetamol were determined in neonates in whom Propacetamol was repeatedly administered. Methods: Paracetamol glucuronide (APAP-G), paracetamol sulphate (APAP-S) and free paracetamol were determined in urine samples of neonates during repeated administration of Propacetamol. Spearman rank and linear multiple regression (MedCalc®, Mariakerke, Belgium) were used to study the effect of postnatal age, of postconceptional age and of repeated administration on the relative contribution of APAP-G to overall urine paracetamol (APAP-G + APAP-S + free paracetamol) elimination (G/T ratio). Results: 147 samples were collected in 23 neonates. Molar median G/T ratio was 14% (range 1-53). Besides increasing G/T ratio with increasing postnatal (p< 0.0001) and postconceptional age (p < 0.01), repeated administration (p < 0.01) also correlated with an increasing G/T ratio, and repeated administration remained significant (p
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intra and interindividual variability of glucuronidation of paracetamol during repeated administration of Propacetamol in neonates
Acta Paediatrica, 2007Co-Authors: Karel Allegaert, Christine Vanhole, Hugo Devlieger, Rene Verbesselt, J De Hoon, Dick TibboelAbstract:Background: Major changes in drug clearance and metabolism are observed during infancy, in part based on ontogenic regulation of various metabolic pathways. Since paracetamol provides a good substrate to study UGT (1A6) activity, urinary metabolites of Propacetamol were determined in neonates in whom Propacetamol was repeatedly administered. Methods: Paracetamol glucuronide (APAP-G), paracetamol sulphate (APAP-S) and free paracetamol were determined in urine samples of neonates during repeated administration of Propacetamol. Spearman rank and linear multiple regression (MedCalc®, Mariakerke, Belgium) were used to study the effect of postnatal age, of postconceptional age and of repeated administration on the relative contribution of APAP-G to overall urine paracetamol (APAP-G + APAP-S + free paracetamol) elimination (G/T ratio). Results: 147 samples were collected in 23 neonates. Molar median G/T ratio was 14% (range 1-53). Besides increasing G/T ratio with increasing postnatal (p< 0.0001) and postconceptional age (p < 0.01), repeated administration (p < 0.01) also correlated with an increasing G/T ratio, and repeated administration remained significant (p<0.01) after correction of postnatal and postconceptional age in a multiple regression model. Conclusion: Major variability in the ontogeny of UGT activity to overall elimination of paracetamol was documented in neonates. Besides postnatal and postconceptional age, a significant effect of repeated administration on UGT activity was documented.
Barbara Poblete - One of the best experts on this subject based on the ideXlab platform.
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metabolic effects of i v Propacetamol metamizol or external cooling in critically ill febrile sedated patients
BJA: British Journal of Anaesthesia, 1997Co-Authors: Barbara Poblete, P. König, Jacques-a Romand, Claude Pichard, Paolo M. SuterAbstract:We have measured the metabolic response to sequential administration of Propacetamol, metamizol and/or external cooling in 20 febrile patients under sedation and analgesia and during mechanical ventilation. There was no change in temperature (T degree) after Propacetamol therapy, whereas after metamizol only a small decrease was noted (from 38.9 (SEM 0.2) to 38.5 (0.3) degrees C; P = 0.02). External cooling produced a significant decrease in T degree (39.1 (0.2) to 37.1 (0.2) degrees C; P
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Metabolic effects of i.v. Propacetamol, metamizol or external cooling in critically ill febrile sedated patients
British Journal of Anaesthesia, 1997Co-Authors: Barbara Poblete, P. König, Jacques-a Romand, Claude Pichard, Paolo M. SuterAbstract:We have measured the metabolic response to sequential administration of Propacetamol, metamizol and/or external cooling in 20 febrile patients under sedation and analgesia and during mechanical ventilation. There was no change in temperature (T degree) after Propacetamol therapy, whereas after metamizol only a small decrease was noted (from 38.9 (SEM 0.2) to 38.5 (0.3) degrees C; P = 0.02). External cooling produced a significant decrease in T degree (39.1 (0.2) to 37.1 (0.2) degrees C; P < 0.0001) accompanied by a decrease in energy expenditure (EE) (2034 (73) to 1791 (88) kcal day-1; P < 0.004). Heart rate and minute ventilation decreased significantly in parallel. There were no other changes in haemodynamics or pulmonary gas exchanges. We conclude that Propacetamol and metamizol did not produce a clinically significant decrease in T degree in febrile ICU patients whereas external cooling decreased both T degree and EE. The parallel decrease in body temperature and EE seemed to be related to opioid administration or sedation, or both.
