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Tawfiq Arafat - One of the best experts on this subject based on the ideXlab platform.
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Saliva versus Plasma Bioequivalence of Valsartan/Hydrochlorothiazide in Humans: Validation of Classes II and IV Drugs of the Salivary Excretion Classification System.
Drug Research, 2020Co-Authors: Nasir Idkaidek, Haneen Agha, Tawfiq ArafatAbstract:Aim The aim of this study is to investigate the robustness of using non-invasive saliva instead of plasma for bioequivalence of valsartan and hydrochlorothiazide (HCT) in humans based on Salivary Excretion Classification System (SECS). Methods Plasma and resting saliva samples were collected over 24 h after oral administration of single dose 160 mg valsartan and 12.5 mg HCT to 12 healthy male volunteers after 10 h overnight fasting. Plasma and saliva concentrations were determined by validated liquid chromatography-mass spectrometry. WinNonlin program V5.2 was used to determine pharmacokinetic parameters and bioequivalence metrics. Moreover, optimized effective intestinal permeability was estimated using PK-Sim/Mobi program V5.6. Results and Discussion Valsartan is SECS class IV drug due of low permeability and high protein binding and hence didn’t appear in saliva. However, HCT is SECS class II drug due to low permeability and low protein binding. No significant differences were observed in the pharmacokinetic parameters in both plasma matrix and saliva matrix (P˃0.05). The 90% confidence intervals did not pass in all parameters due to the high intra-subject variability and small sample size used in this study. Saliva to plasma ratios of HCT were low, yet with high correlation coefficient of 0.96–0.98. So saliva can be used as alternative to plasma sample in pharmacokinetic studies and in bioequivalence when adequate sample size is used.
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saliva versus plasma bioequivalence of valsartan hydrochlorothiazide in humans validation of classes ii and iv drugs of the Salivary Excretion classification system
Drug Research, 2018Co-Authors: Nasir Idkaidek, Haneen Agha, Tawfiq ArafatAbstract:Aim The aim of this study is to investigate the robustness of using non-invasive saliva instead of plasma for bioequivalence of valsartan and hydrochlorothiazide (HCT) in humans based on Salivary Excretion Classification System (SECS). Methods Plasma and resting saliva samples were collected over 24 h after oral administration of single dose 160 mg valsartan and 12.5 mg HCT to 12 healthy male volunteers after 10 h overnight fasting. Plasma and saliva concentrations were determined by validated liquid chromatography-mass spectrometry. WinNonlin program V5.2 was used to determine pharmacokinetic parameters and bioequivalence metrics. Moreover, optimized effective intestinal permeability was estimated using PK-Sim/Mobi program V5.6. Results and Discussion Valsartan is SECS class IV drug due of low permeability and high protein binding and hence didn’t appear in saliva. However, HCT is SECS class II drug due to low permeability and low protein binding. No significant differences were observed in the pharmacokinetic parameters in both plasma matrix and saliva matrix (P˃0.05). The 90% confidence intervals did not pass in all parameters due to the high intra-subject variability and small sample size used in this study. Saliva to plasma ratios of HCT were low, yet with high correlation coefficient of 0.96–0.98. So saliva can be used as alternative to plasma sample in pharmacokinetic studies and in bioequivalence when adequate sample size is used.
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Saliva versus Plasma Bioequivalence of Valsartan/Hydrochlorothiazide in Humans: Validation of Classes II and IV Drugs of the Salivary Excretion Classification System.
Drug research, 2017Co-Authors: Nasir Idkaidek, Haneen Agha, Tawfiq ArafatAbstract:The aim of this study is to investigate the robustness of using non-invasive saliva instead of plasma for bioequivalence of valsartan and hydrochlorothiazide (HCT) in humans based on Salivary Excretion Classification System (SECS). Plasma and resting saliva samples were collected over 24 h after oral administration of single dose 160 mg valsartan and 12.5 mg HCT to 12 healthy male volunteers after 10 h overnight fasting. Plasma and saliva concentrations were determined by validated liquid chromatography-mass spectrometry. WinNonlin program V5.2 was used to determine pharmacokinetic parameters and bioequivalence metrics. Moreover, optimized effective intestinal permeability was estimated using PK-Sim/Mobi program V5.6. Valsartan is SECS class IV drug due of low permeability and high protein binding and hence didn't appear in saliva. However, HCT is SECS class II drug due to low permeability and low protein binding. No significant differences were observed in the pharmacokinetic parameters in both plasma matrix and saliva matrix (P˃0.05). The 90% confidence intervals did not pass in all parameters due to the high intra-subject variability and small sample size used in this study. Saliva to plasma ratios of HCT were low, yet with high correlation coefficient of 0.96-0.98. So saliva can be used as alternative to plasma sample in pharmacokinetic studies and in bioequivalence when adequate sample size is used. © Georg Thieme Verlag KG Stuttgart · New York.
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Saliva Versus Plasma Bioequivalence of Azithromycin in Humans: Validation of Class I Drugs of the Salivary Excretion Classification System.
Drugs in R&D, 2017Co-Authors: Nasir Idkaidek, Tawfiq Arafat, Hazim Hamadi, Salim Hamadi, Ibrahim Al-adhamAbstract:The aim of this study was to compare human pharmacokinetics and bioequivalence metrics in saliva versus plasma for azithromycin as a model class I drug of the Salivary Excretion Classification System (SECS). A pilot, open-label, two-way crossover bioequivalence study was done, and involved a single 500-mg oral dose of azithromycin given to eight healthy subjects under fasting conditions, followed by a 3-week washout period. Blood and unstimulated saliva samples were collected over 72 h and deep frozen until analysis by a validated liquid chromatography with mass spectroscopy method. The pharmacokinetic parameters and bioequivalence metrics of azithromycin were calculated by non-compartment analysis using WinNonlin V5.2. Descriptive statistics and dimensional analysis of the pharmacokinetic parameters of azithromycin were performed using Microsoft Excel. PK-Sim V5.6 was used to estimate the effective intestinal permeability of azithromycin. No statistical differences were shown in area under the concentration curves to 72 h (AUC0-72), maximum measured concentration (C max) and time to maximum concentration (T max) between test and reference azithromycin products (P > 0.05) in the saliva matrix and in the plasma matrix. Due to the high intra-subject variability and low sample size of this pilot study, the 90% confidence intervals of AUC0-72 and C max did not fall within the acceptance range (80-125%). However, saliva levels were higher than that of plasma, with a longer Salivary T max. The mean saliva/plasma concentration of test and reference were 2.29 and 2.33, respectively. The mean ± standard deviation ratios of saliva/plasma of AUC0-72, C max and T max for test were 2.65 ± 1.59, 1.51 ± 0.49 and 1.85 ± 1.4, while for the reference product they were 3.37 ± 2.20, 1.57 ± 0.77 and 2.6 ± 1.27, respectively. A good correlation of R = 0.87 between plasma and saliva concentrations for both test and reference products was also observed. Azithromycin is considered a class I drug based on the SECS, since it has a high permeability and high fraction unbound, and saliva sampling could be used as an alternative to plasma sampling to characterize its pharmacokinetics and bioequivalence in humans when adequate sample size is used.
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Saliva Versus Plasma Bioequivalence of Rusovastatin in Humans: Validation of Class III Drugs of the Salivary Excretion Classification System
Drugs in R&D, 2015Co-Authors: Nasir Idkaidek, Tawfiq ArafatAbstract:Bioequivalence of rusovastatin in healthy human volunteers was done using saliva and plasma matrices in order to investigate the robustness of using saliva instead of plasma as a surrogate for bioequivalence of class III drugs according to the Salivary Excretion classification system (SECS). Saliva and plasma samples were collected for 72 h after oral administration of rusovastatin 40 mg to 12 healthy humans. Saliva and plasma pharmacokinetic parameters were calculated by non-compartmental analysis. Analysis of variance, 90 % confidence intervals, and intra-subject and inter-subject variability values of pharmacokinetic parameters were calculated using Kinetica program V5. Human effective intestinal permeability was also calculated by SimCYP program V13. Rusovastatin falls into class III (high permeability/low fraction unbound to plasma proteins) and hence was subjected to Salivary Excretion. A correlation coefficient of 0.99 between saliva and plasma concentrations, and a saliva/plasma concentration ratio of 0.175 were observed. The 90 % confidence limits of area under the curve (AUC_last) and maximum concentration ( C _max) showed similar trends in both saliva and plasma. On the other hand, inter- and intra-subject variability values in saliva were higher than in plasma, leading to the need for a slightly higher number of subjects to be used in saliva studies. Non-invasive saliva sampling instead of the invasive plasma sampling method can be used as a surrogate for bioequivalence of SECS class III drugs when an adequate sample size is used.
Nasir Idkaidek - One of the best experts on this subject based on the ideXlab platform.
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Saliva versus Plasma Bioequivalence of Valsartan/Hydrochlorothiazide in Humans: Validation of Classes II and IV Drugs of the Salivary Excretion Classification System.
Drug Research, 2020Co-Authors: Nasir Idkaidek, Haneen Agha, Tawfiq ArafatAbstract:Aim The aim of this study is to investigate the robustness of using non-invasive saliva instead of plasma for bioequivalence of valsartan and hydrochlorothiazide (HCT) in humans based on Salivary Excretion Classification System (SECS). Methods Plasma and resting saliva samples were collected over 24 h after oral administration of single dose 160 mg valsartan and 12.5 mg HCT to 12 healthy male volunteers after 10 h overnight fasting. Plasma and saliva concentrations were determined by validated liquid chromatography-mass spectrometry. WinNonlin program V5.2 was used to determine pharmacokinetic parameters and bioequivalence metrics. Moreover, optimized effective intestinal permeability was estimated using PK-Sim/Mobi program V5.6. Results and Discussion Valsartan is SECS class IV drug due of low permeability and high protein binding and hence didn’t appear in saliva. However, HCT is SECS class II drug due to low permeability and low protein binding. No significant differences were observed in the pharmacokinetic parameters in both plasma matrix and saliva matrix (P˃0.05). The 90% confidence intervals did not pass in all parameters due to the high intra-subject variability and small sample size used in this study. Saliva to plasma ratios of HCT were low, yet with high correlation coefficient of 0.96–0.98. So saliva can be used as alternative to plasma sample in pharmacokinetic studies and in bioequivalence when adequate sample size is used.
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saliva versus plasma bioequivalence of valsartan hydrochlorothiazide in humans validation of classes ii and iv drugs of the Salivary Excretion classification system
Drug Research, 2018Co-Authors: Nasir Idkaidek, Haneen Agha, Tawfiq ArafatAbstract:Aim The aim of this study is to investigate the robustness of using non-invasive saliva instead of plasma for bioequivalence of valsartan and hydrochlorothiazide (HCT) in humans based on Salivary Excretion Classification System (SECS). Methods Plasma and resting saliva samples were collected over 24 h after oral administration of single dose 160 mg valsartan and 12.5 mg HCT to 12 healthy male volunteers after 10 h overnight fasting. Plasma and saliva concentrations were determined by validated liquid chromatography-mass spectrometry. WinNonlin program V5.2 was used to determine pharmacokinetic parameters and bioequivalence metrics. Moreover, optimized effective intestinal permeability was estimated using PK-Sim/Mobi program V5.6. Results and Discussion Valsartan is SECS class IV drug due of low permeability and high protein binding and hence didn’t appear in saliva. However, HCT is SECS class II drug due to low permeability and low protein binding. No significant differences were observed in the pharmacokinetic parameters in both plasma matrix and saliva matrix (P˃0.05). The 90% confidence intervals did not pass in all parameters due to the high intra-subject variability and small sample size used in this study. Saliva to plasma ratios of HCT were low, yet with high correlation coefficient of 0.96–0.98. So saliva can be used as alternative to plasma sample in pharmacokinetic studies and in bioequivalence when adequate sample size is used.
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Saliva versus Plasma Bioequivalence of Valsartan/Hydrochlorothiazide in Humans: Validation of Classes II and IV Drugs of the Salivary Excretion Classification System.
Drug research, 2017Co-Authors: Nasir Idkaidek, Haneen Agha, Tawfiq ArafatAbstract:The aim of this study is to investigate the robustness of using non-invasive saliva instead of plasma for bioequivalence of valsartan and hydrochlorothiazide (HCT) in humans based on Salivary Excretion Classification System (SECS). Plasma and resting saliva samples were collected over 24 h after oral administration of single dose 160 mg valsartan and 12.5 mg HCT to 12 healthy male volunteers after 10 h overnight fasting. Plasma and saliva concentrations were determined by validated liquid chromatography-mass spectrometry. WinNonlin program V5.2 was used to determine pharmacokinetic parameters and bioequivalence metrics. Moreover, optimized effective intestinal permeability was estimated using PK-Sim/Mobi program V5.6. Valsartan is SECS class IV drug due of low permeability and high protein binding and hence didn't appear in saliva. However, HCT is SECS class II drug due to low permeability and low protein binding. No significant differences were observed in the pharmacokinetic parameters in both plasma matrix and saliva matrix (P˃0.05). The 90% confidence intervals did not pass in all parameters due to the high intra-subject variability and small sample size used in this study. Saliva to plasma ratios of HCT were low, yet with high correlation coefficient of 0.96-0.98. So saliva can be used as alternative to plasma sample in pharmacokinetic studies and in bioequivalence when adequate sample size is used. © Georg Thieme Verlag KG Stuttgart · New York.
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Saliva Versus Plasma Bioequivalence of Azithromycin in Humans: Validation of Class I Drugs of the Salivary Excretion Classification System.
Drugs in R&D, 2017Co-Authors: Nasir Idkaidek, Tawfiq Arafat, Hazim Hamadi, Salim Hamadi, Ibrahim Al-adhamAbstract:The aim of this study was to compare human pharmacokinetics and bioequivalence metrics in saliva versus plasma for azithromycin as a model class I drug of the Salivary Excretion Classification System (SECS). A pilot, open-label, two-way crossover bioequivalence study was done, and involved a single 500-mg oral dose of azithromycin given to eight healthy subjects under fasting conditions, followed by a 3-week washout period. Blood and unstimulated saliva samples were collected over 72 h and deep frozen until analysis by a validated liquid chromatography with mass spectroscopy method. The pharmacokinetic parameters and bioequivalence metrics of azithromycin were calculated by non-compartment analysis using WinNonlin V5.2. Descriptive statistics and dimensional analysis of the pharmacokinetic parameters of azithromycin were performed using Microsoft Excel. PK-Sim V5.6 was used to estimate the effective intestinal permeability of azithromycin. No statistical differences were shown in area under the concentration curves to 72 h (AUC0-72), maximum measured concentration (C max) and time to maximum concentration (T max) between test and reference azithromycin products (P > 0.05) in the saliva matrix and in the plasma matrix. Due to the high intra-subject variability and low sample size of this pilot study, the 90% confidence intervals of AUC0-72 and C max did not fall within the acceptance range (80-125%). However, saliva levels were higher than that of plasma, with a longer Salivary T max. The mean saliva/plasma concentration of test and reference were 2.29 and 2.33, respectively. The mean ± standard deviation ratios of saliva/plasma of AUC0-72, C max and T max for test were 2.65 ± 1.59, 1.51 ± 0.49 and 1.85 ± 1.4, while for the reference product they were 3.37 ± 2.20, 1.57 ± 0.77 and 2.6 ± 1.27, respectively. A good correlation of R = 0.87 between plasma and saliva concentrations for both test and reference products was also observed. Azithromycin is considered a class I drug based on the SECS, since it has a high permeability and high fraction unbound, and saliva sampling could be used as an alternative to plasma sampling to characterize its pharmacokinetics and bioequivalence in humans when adequate sample size is used.
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saliva versus plasma relative bioavailability of tolterodine in humans validation of class iii drugs of the Salivary Excretion classification system
Drug Research, 2016Co-Authors: Nasir Idkaidek, Naji M Najib, Isam Salem, O NajibAbstract:Relative bioavailability study of tolterodine in healthy human volunteers was done using saliva and plasma matrices in order to investigate the robustness of using saliva instead of plasma as a surrogate for bioavailability and bioequivalence of class III drugs according to the Salivary Excretion classification system (SECS). Saliva and plasma samples were collected up to 16 h after 2 mg oral dose. Saliva and plasma pharmacokinetic parameters were calculated by non compartmental analysis using Kinetica program V5. Human effective intestinal permeability was optimized by SimCYP program V13. Tolterodine falls into class III (High permeability/Low fraction unbound to plasma proteins) and hence was subjected to Salivary Excretion. A high pearsons correlation coefficient of 0.97 between mean saliva and plasma concentrations, and saliva/plasma concentrations ratio of 0.33 were observed. In addition, correlation coefficients and saliva/plasma ratios of area under curve and maximum concentration were 0.98, 0.95 and 0.42, 0.34 respectively. On the other hand, time to reach maximum concentration was higher in saliva by 2.37 fold. In addition, inter subject variability values in saliva were slightly higher than plasma leading to need for slightly higher number of subjects to be used in saliva studies (55 vs. 48 subjects). Non-invasive saliva sampling instead of invasive plasma sampling method can be used as a surrogate for bioavailability and bioequivalence of SECS class I drugs when adequate sample size is used.
Maurizio Mazzoni - One of the best experts on this subject based on the ideXlab platform.
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Effect of dietary addition of nitrate on growth, Salivary and gastric function, immune response, and Excretion ofSalmonella entericaserovar Typhimurium, in weaning pigs challenged with this microbe strain
Italian Journal of Animal Science, 2020Co-Authors: Paolo Bosi, L. Casini, C. Tittarelli, Laura Minieri, S. De Filippi, Paolo Trevisi, Paolo Clavenzani, Maurizio MazzoniAbstract:Two dietary additions of nitrate (15 mg/kg or 150 mg/kg, supplied by potassium salt) were tested in a total 96 weaning pigs challenged or not with Salmonella enterica serovar typhimurium (ST). The oral challenge was done on d 5 and pigs were sacrificed on d 7 or d 25. The effect of challenge never interacted significantly with the dietary treatment. Feed intake, growth, body temperature, Salivary Excretion, and faecal Excretion of ST and gastric function were not affected by the nitrate supplementation. With nitrate additions, total IgA in blood serum tended to be higher before and after the challenge (P
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Effect of dietary addition of nitrate on growth, Salivary and gastric function, immune response, and Excretion of Salmonella enterica serovar Typhimurium, in weaning pigs challenged with this microbe strain
Italian Journal of Animal Science, 2007Co-Authors: Paolo Bosi, L. Casini, C. Tittarelli, Laura Minieri, S. De Filippi, Paolo Trevisi, Paolo Clavenzani, Maurizio MazzoniAbstract:Two dietary additions of nitrate (15 mg/kg or 150 mg/kg, supplied by potassium salt) were tested in a total 96 weaning pigs challenged or not with Salmonella enterica serovar typhimurium (ST). The oral challenge was done on d 5 and pigs were sacrificed on d 7 or d 25. The effect of challenge never interacted significantly with the dietary treatment. Feed intake, growth, body temperature, Salivary Excretion, and faecal Excretion of ST and gastric function were not affected by the nitrate supplementation. With nitrate additions, total IgA in blood serum tended to be higher before and after the challenge (P
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effect of dietary addition of nitrate on growth Salivary and gastric function immune response and Excretion of salmonella enterica serovar typhimurium in weaning pigs challenged with this microbe strain
Italian Journal of Animal Science, 2007Co-Authors: Paolo Bosi, L. Casini, C. Tittarelli, Laura Minieri, S. De Filippi, Paolo Trevisi, Paolo Clavenzani, Maurizio MazzoniAbstract:Two dietary additions of nitrate (15 mg/kg or 150 mg/kg, supplied by potassium salt) were tested in a total 96 weaning pigs challenged or not with Salmonella enterica serovar typhimurium (ST). The oral challenge was done on d 5 and pigs were sacrificed on d 7 or d 25. The effect of challenge never interacted significantly with the dietary treatment. Feed intake, growth, body temperature, Salivary Excretion, and faecal Excretion of ST and gastric function were not affected by the nitrate supplementation. With nitrate additions, total IgA in blood serum tended to be higher before and after the challenge (P<0.10). Nitrite in saliva – but not nitrate – increased with the increasing supplementation at d 5, but not at d 19. The nitrate additions did not negatively affect the weaning performance, but also did not contrast the effect of ST infection.
Ji Won Choi - One of the best experts on this subject based on the ideXlab platform.
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a prospective randomized comparison of the effects of inhaled sevoflurane anesthesia and propofol remifentanil intravenous anesthesia on Salivary Excretion during laryngeal microsurgery
Anesthesia & Analgesia, 2008Co-Authors: Jin Gu Kang, Hansin Jeong, Soochan Jung, Moon Hee Ko, Shin Hong Park, Ji Won ChoiAbstract:BACKGROUND: One of the goals of anesthesia for laryngeal microsurgery is to provide a clear surgical view, and therefore anesthetics that produce less saliva are desirable. Sevoflurane inhalation anesthesia and total IV anesthesia with propofol/remifentanil are widely used for anesthesia during laryngeal microsurgery; however, few rigorous comparisons of the effects of sevoflurane and propofol/remifentanil on salivation have been performed. METHODS: Forty subjects undergoing laryngeal microsurgery were randomly assigned for sevoflurane or propofol/remifentanil anesthesia. We prospectively compared the Salivary flow rates, compositions, the number of suction episodes required to clearly view the laryngeal lesions before the main procedures, and residual secretion volume after the procedure in both groups. RESULTS: The mean Salivary Excretion rate was significantly higher in the propofol/remifentanil group than in the sevoflurane group (0.53 +/- 0.39 vs 0.28 +/- 0.15 mL/min, P < 0.001). Before starting the main procedure, the number of suction episodes required to clearly view the laryngeal lesions was also higher in the propofol/remifentanil group (5.0 +/- 2.3 vs 2.1 +/- 1.5, P < 0.001). Mean residual secretion in the oral cavity and oropharynx after the procedure was greater in the propofol/remifentanil group (2.13 +/- 0.59 vs 0.45 +/- 0.32 mL, P < 0.001). In addition, a significant difference in chloride levels in collected secretion was noted (sevoflurane; 93 +/- 19 vs propofol/remifentanil; 135 +/- 58 U/L, P = 0.004). CONCLUSIONS: Salivary Excretion under propofol/remifentanil anesthesia is greater than under sevoflurane anesthesia during laryngeal surgery.
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A prospective, randomized comparison of the effects of inhaled sevoflurane anesthesia and propofol/remifentanil intravenous anesthesia on Salivary Excretion during laryngeal microsurgery.
Anesthesia & Analgesia, 2008Co-Authors: Jin Gu Kang, Hansin Jeong, Soochan Jung, Moon Hee Ko, Shin Hong Park, Ji Won ChoiAbstract:BACKGROUND: One of the goals of anesthesia for laryngeal microsurgery is to provide a clear surgical view, and therefore anesthetics that produce less saliva are desirable. Sevoflurane inhalation anesthesia and total IV anesthesia with propofol/remifentanil are widely used for anesthesia during laryngeal microsurgery; however, few rigorous comparisons of the effects of sevoflurane and propofol/remifentanil on salivation have been performed. METHODS: Forty subjects undergoing laryngeal microsurgery were randomly assigned for sevoflurane or propofol/remifentanil anesthesia. We prospectively compared the Salivary flow rates, compositions, the number of suction episodes required to clearly view the laryngeal lesions before the main procedures, and residual secretion volume after the procedure in both groups. RESULTS: The mean Salivary Excretion rate was significantly higher in the propofol/remifentanil group than in the sevoflurane group (0.53 +/- 0.39 vs 0.28 +/- 0.15 mL/min, P < 0.001). Before starting the main procedure, the number of suction episodes required to clearly view the laryngeal lesions was also higher in the propofol/remifentanil group (5.0 +/- 2.3 vs 2.1 +/- 1.5, P < 0.001). Mean residual secretion in the oral cavity and oropharynx after the procedure was greater in the propofol/remifentanil group (2.13 +/- 0.59 vs 0.45 +/- 0.32 mL, P < 0.001). In addition, a significant difference in chloride levels in collected secretion was noted (sevoflurane; 93 +/- 19 vs propofol/remifentanil; 135 +/- 58 U/L, P = 0.004). CONCLUSIONS: Salivary Excretion under propofol/remifentanil anesthesia is greater than under sevoflurane anesthesia during laryngeal surgery.
Gideon Koren - One of the best experts on this subject based on the ideXlab platform.
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Salivary Excretion of drugs in children theoretical and practical issues in therapeutic drug monitoring
Developmental pharmacology and therapeutics, 1992Co-Authors: Rafael Gorodischer, Gideon KorenAbstract:: Studies suggest that saliva could be used instead of blood in the therapeutic monitoring of many drugs. This has distinct advantages in pediatrics and neonatology as saliva sampling is painless and spares blood. Stimulation of saliva secretion with a chemical stimulus (i.e. citric acid applied over the tongue) facilitates the study of younger patients. Secretory and reabsorptive processes which take place in the ductal system of the Salivary glands, and the rate of flow of the secretion play major roles in the determination of the concentration of solutes in saliva. Drug passage into saliva follows the general principles of movement of drugs across biologic membranes. Only the unbound fraction of the drug in plasma is available for diffusion into saliva and a relationship exists between saliva pH and the saliva/plasma concentration ratio of many polar drugs (tolbutamide, propranolol, procainamide, etc.). However, deviations from the pH theory exist and the inter -and intra-individual variations in saliva/plasma concentration ratios of salicylate and procainamide cannot be explained solely on the basis of fluctuations of Salivary pH; on the other hand, a useful relationship exists between plasma and saliva phenobarbital concentrations with no need to correct for saliva pH. The use of stimulated saliva has several advantages over resting saliva: a larger volume of the sample is obtained, the pH gradient between plasma and saliva is smaller, the variability in saliva/plasma concentration ratios of some drugs is narrowed, and less specimens are too viscous or discolored to allow drug analysis. Thorough rinsing of the mouth is required prior to saliva sampling as remnants of orally administered medicines may contaminate saliva specimens and give spuriously high values. Deviation from a simple but strict methodology accounts for some of the discrepancies found in the literature. Studies in children uniformly recommend saliva for therapeutic monitoring of phenytoin, carbamazepine and phenobarbital. Saliva sampling for therapeutic monitoring of ethosuximide, primidone and digoxin in infants and children, and of theophylline and caffeine in the neonate is promising, but little pediatric experience is available as yet. The value of saliva in therapeutic monitoring of theophylline in children is still controversial. Little of highly polar compounds such as aminoglycosides, and of polar highly protein bound drugs such as valproic acid is present in saliva. More data are still needed on the Excretion of drugs in saliva in infants and in acutely ill children, and few data exist in the premature and full-term neonate.
