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Nele Samyn - One of the best experts on this subject based on the ideXlab platform.
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detection of Diazepam in urine hair and preserved oral fluid samples with lc ms ms after single and repeated administration of myolastan and valium
Analytical and Bioanalytical Chemistry, 2007Co-Authors: Marleen Laloup, Maria Del Mar Ramirez Fernandez, Michelle Wood, Viviane Maes, Gert De Boeck, Yvan Vanbeckevoort, Nele SamynAbstract:Sedative agents are used to facilitate sexual assault due to their ability to render the victim passive, submissive and unable to resist. The primary pharmacological effect of the benzodiazepine tetrazepam is muscle relaxation, whereas the benzodiazepine Diazepam acts on the central nervous system (CNS) exerting mainly sedation effects. Therefore, contrary to tetrazepam, Diazepam is an often-abused drug, which can potentially be used as a date-rape drug. In this study, we describe the detection of low amounts of Diazepam in Myolastan® (Sanofi–Synthelabo S.A., Brussels, Belgium) and Epsipam® (Will-Pharma, Wavre, Belgium) 50mg tablet preparations by LC-MS-MS, GC-FID and HPLC-DAD. Considering the important forensic implication of this finding, a study was conducted with volunteers receiving a single or repeated dosage of Myolastan®. Urine, hair and preserved oral fluid samples were analysed using a previously described sensitive and specific LC-MS-MS detection method allowing for the simultaneous quantification of tetrazepam, Diazepam, norDiazepam, oxazepam and temazepam. This study demonstrates that Diazepam can be observed in urine samples even after a single dose of Myolastan®. In addition, maintaining therapy for 1 week results in the detection of both Diazepam and norDiazepam in urine samples and of Diazepam in the first hair segment. Importantly, comparing urine and hair samples after a single intake of Diazepam versus the single and 1 week administration of Myolastan® shows that the possible metabolic conversion of tetrazepam to Diazepam is a more plausible explanation for the detection of Diazepam in biological samples after the intake of Myolastan®. As such, these results reveal that the presence of Diazepam and/or norDiazepam in biological samples from alleged drug-facilitated assault cases should be interpreted with care.
Sriram Krishnamurthy - One of the best experts on this subject based on the ideXlab platform.
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lorazepam versus Diazepam phenytoin combination in the treatment of convulsive status epilepticus in children a randomized controlled trial
European Journal of Paediatric Neurology, 2010Co-Authors: T G Sreenath, Piyush Gupta, Kapil Sharma, Sriram KrishnamurthyAbstract:Abstract Background Convulsive status epilepticus demands urgent and appropriate management with anticonvulsants. Intravenous Diazepam is an established drug in the management of convulsive status epilepticus in adults as well as in children. The efficacy of intravenous lorazepam has not been well established in children. Objective To determine whether intravenous lorazepam is as efficacious as Diazepam–phenytoin combination in the treatment of convulsive status epilepticus in children. Study design Randomized controlled trial. Methods A total of 178 children were enrolled in the study; 90 in the lorazepam group and 88 in the Diazepam–phenytoin combination group. Enrolled subjects were between 1 and 12 years with a clinical diagnosis of convulsive status epilepticus, presenting in pediatric emergency of a tertiary care hospital. They were randomized to receive either intravenous lorazepam (0.1 mg/kg) or intravenous Diazepam (0.2 mg/kg)–phenytoin (18 mg/kg) combination at admission and were followed up for subsequent 18 h. Results The overall success rate of therapy was 100% in both the groups. There was no statistically significant difference in the two groups (lorazepam versus Diazepam–phenytoin combination) in the median time taken to stop the seizure [20 s in both groups], the number of subjects requiring more than one dose of the study drug to stop the presenting seizure [lorazepam 6(6.7%) versus Diazepam–phenytoin combination: 14 (15.9%); adjusted RR (95% CI) = 0.377 (0.377, 1.046); P = 0.061] and the number (%) of patients having respiratory depression [lorazepam 4(4.4%) versus Diazepam–phenytoin combination 5 (5.6%)]. None of the patients in the two groups required additional anticonvulsant drug to stop the presenting seizure. No patient required mechanical ventilation and none of the patients in the two groups required cross-over to the alternative regimen. Conclusion Lorazepam is as efficacious and safe as Diazepam–phenytoin combination. We recommend use of lorazepam as a single drug to replace the two drug combination of Diazepam–phenytoin combination to control the initial seizure in pediatric convulsive status epilepticus.
Henderik W Frijlink - One of the best experts on this subject based on the ideXlab platform.
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characterization of the molecular distribution of drugs in glassy solid dispersions at the nano meter scale using differential scanning calorimetry and gravimetric water vapour sorption techniques
International Journal of Pharmaceutics, 2006Co-Authors: D J Van Drooge, Wouter L J Hinrichs, Marinella R Visser, Henderik W FrijlinkAbstract:Abstract The molecular distribution in fully amorphous solid dispersions consisting of poly(vinylpyrrolidone) (PVP)–Diazepam and inulin–Diazepam was studied. One glass transition temperature ( T g ), as determined by temperature modulated differential scanning calorimetry (TMDSC), was observed in PVP–Diazepam solid dispersions prepared by fusion for all drug loads tested (10–80 wt.%). The T g of these solid dispersions gradually changed with composition and decreased from 177 °C for pure PVP to 46 °C for Diazepam. These observations indicate that Diazepam was dispersed in PVP on a molecular level. However, in PVP–Diazepam solid dispersions prepared by freeze drying, two T g 's were observed for drug loads above 35 wt.% indicating phase separation. One T g indicated the presence of amorphous Diazepam clusters, the other T g was attributed to a PVP-rich phase in which Diazepam was dispersed on a molecular level. With both the value of the latter T g and the Δ C p of the Diazepam glass transition the concentrations of molecular dispersed Diazepam could be calculated (27–35 wt.%). Both methods gave similar results. Water vapour sorption (DVS) experiments revealed that the PVP-matrix was hydrophobised by the incorporated Diazepam. TMDSC and DVS results were used to estimate the size of Diazepam clusters in freeze dried PVP–Diazepam solid dispersions, which appeared to be in the nano-meter range. The inulin–Diazepam solid dispersions prepared by spray freeze drying showed one T g for drug loads up to 35 wt.% indicating homogeneous distribution on a molecular level. However, this T g was independent of the drug load, which is unexpected because Diazepam has a lower T g than inulin (46 and 155 °C, respectively). For higher drug loads, a T g of Diazepam as well as a T g of the inulin-rich phase was observed, indicating the formation of amorphous Diazepam clusters. From the Δ C p of the Diazepam glass transition the amount of molecularly dispersed Diazepam was calculated (12–27 wt.%). In contrast to the PVP–Diazepam solid dispersions, DVS-experiments revealed that inulin was not hydrophobised by Diazepam. Consequently, the size of Diazepam clusters could not be estimated. It was concluded that TMDSC enables characterization and quantification of the molecular distribution in amorphous solid dispersions. When the hygroscopicity of the carrier is reduced by the drug, DVS in combination with TMDSC can be used to estimate the size of amorphous drug clusters.
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characterization of the molecular distribution of drugs in glassy solid dispersions at the nano meter scale using differential scanning calorimetry and gravimetric water vapour sorption techniques
International Journal of Pharmaceutics, 2006Co-Authors: D J Van Drooge, Wouter L J Hinrichs, Marinella R Visser, Henderik W FrijlinkAbstract:The molecular distribution in fully amorphous solid dispersions consisting of poly(vinylpyrrolidone) (PVP)-Diazepam and inulin-Diazepam was studied. One glass transition temperature (T(g)), as determined by temperature modulated differential scanning calorimetry (TMDSC), was observed in PVP-Diazepam solid dispersions prepared by fusion for all drug loads tested (10-80 wt.%). The T(g) of these solid dispersions gradually changed with composition and decreased from 177 degrees C for pure PVP to 46 degrees C for Diazepam. These observations indicate that Diazepam was dispersed in PVP on a molecular level. However, in PVP-Diazepam solid dispersions prepared by freeze drying, two T(g)'s were observed for drug loads above 35 wt.% indicating phase separation. One T(g) indicated the presence of amorphous Diazepam clusters, the other T(g) was attributed to a PVP-rich phase in which Diazepam was dispersed on a molecular level. With both the value of the latter T(g) and the DeltaC(p) of the Diazepam glass transition the concentrations of molecular dispersed Diazepam could be calculated (27-35 wt.%). Both methods gave similar results. Water vapour sorption (DVS) experiments revealed that the PVP-matrix was hydrophobised by the incorporated Diazepam. TMDSC and DVS results were used to estimate the size of Diazepam clusters in freeze dried PVP-Diazepam solid dispersions, which appeared to be in the nano-meter range. The inulin-Diazepam solid dispersions prepared by spray freeze drying showed one T(g) for drug loads up to 35 wt.% indicating homogeneous distribution on a molecular level. However, this T(g) was independent of the drug load, which is unexpected because Diazepam has a lower T(g) than inulin (46 and 155 degrees C, respectively). For higher drug loads, a T(g) of Diazepam as well as a T(g) of the inulin-rich phase was observed, indicating the formation of amorphous Diazepam clusters. From the DeltaC(p) of the Diazepam glass transition the amount of molecularly dispersed Diazepam was calculated (12-27 wt.%). In contrast to the PVP-Diazepam solid dispersions, DVS-experiments revealed that inulin was not hydrophobised by Diazepam. Consequently, the size of Diazepam clusters could not be estimated. It was concluded that TMDSC enables characterization and quantification of the molecular distribution in amorphous solid dispersions. When the hygroscopicity of the carrier is reduced by the drug, DVS in combination with TMDSC can be used to estimate the size of amorphous drug clusters.
Shannon K Laughlintommaso - One of the best experts on this subject based on the ideXlab platform.
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vaginal Diazepam for nonrelaxing pelvic floor dysfunction the pharmacokinetic profile
The Journal of Sexual Medicine, 2019Co-Authors: Alyssa Larish, Rozalin R Dickson, Rachel A Kudgus, Renee M Mcgovern, Joel M Reid, Michael W Hooten, Wayne T Nicholson, Lisa E Vaughan, Tatnai L Burnett, Shannon K LaughlintommasoAbstract:Abstract Background Vaginal Diazepam is frequently used to treat pelvic floor tension myalgia and pelvic pain despite limited knowledge of systemic absorption. Aim To determine the pharmacokinetic and adverse event profile of Diazepam vaginal suppositories. Methods We used a prospective pharmacokinetic design with repeated assessments of Diazepam levels. Eight healthy volunteers were administered a 10-mg compounded vaginal Diazepam suppository in the outpatient gynecologic clinic. Serum samples were collected at 0, 45, 90, 120, and 180 minutes; 8, 24, and 72 hours; and 1 week following administration of a 10-mg vaginal suppository. The occurrence of adverse events was assessed using the alternate step and tandem walk tests, the Brief Confusion Assessment Method, and numerical ratings. Plasma concentrations of Diazepam and active long-acting metabolites were measured. Pharmacokinetic parameters were calculated by standard noncompartmental methods. Results The mean peak Diazepam concentration (Cmax) of 31.0 ng/mL was detected at a mean time (Tmax) of 3.1 hours after suppository placement. The bioavailability was found to be 70.5%, and the mean terminal elimination half-life was 82 hours. The plasma levels of temazepam and norDiazepam peaked at 0.8 ng/mL at 29 hours and 6.4 ng/mL at 132 hours, respectively. Fatigue was reported by 3 of 8 participants. Clinical Implications Serum plasma concentrations of vaginally administered Diazepam are low; however the half-life is prolonged. Strengths & Limitations Strengths include use of inclusion and exclusion criteria aimed at mitigating clinical factors that could adversely impact Diazepam absorption and metabolism, and the use of an ultrasensitive LC-MS/MS assay. Limitations included the lack of addressing the efficacy of vaginal Diazepam in lieu of performing a pure pharmacokinetic study with healthy participants. Conclusion Vaginal administration of Diazepam results in lower peak serum plasma concentration, longer time to peak concentration, and lower bioavailability than standard oral use. Providers should be aware that with Diazepam’s long half-life, accumulating levels would occur with chronic daily doses, and steady-state levels would not be reached for up to 1 week. This profile would favor intermittent use to allow participation in physical therapy and intimacy. Larish AM, Dickson RR, Kudgus RA, et al. Vaginal Diazepam for Nonrelaxing Pelvic Floor Dysfunction: The Pharmacokinetic Profile. J Sex Med 2019;16;763–766.
Marleen Laloup - One of the best experts on this subject based on the ideXlab platform.
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detection of Diazepam in urine hair and preserved oral fluid samples with lc ms ms after single and repeated administration of myolastan and valium
Analytical and Bioanalytical Chemistry, 2007Co-Authors: Marleen Laloup, Maria Del Mar Ramirez Fernandez, Michelle Wood, Viviane Maes, Gert De Boeck, Yvan Vanbeckevoort, Nele SamynAbstract:Sedative agents are used to facilitate sexual assault due to their ability to render the victim passive, submissive and unable to resist. The primary pharmacological effect of the benzodiazepine tetrazepam is muscle relaxation, whereas the benzodiazepine Diazepam acts on the central nervous system (CNS) exerting mainly sedation effects. Therefore, contrary to tetrazepam, Diazepam is an often-abused drug, which can potentially be used as a date-rape drug. In this study, we describe the detection of low amounts of Diazepam in Myolastan® (Sanofi–Synthelabo S.A., Brussels, Belgium) and Epsipam® (Will-Pharma, Wavre, Belgium) 50mg tablet preparations by LC-MS-MS, GC-FID and HPLC-DAD. Considering the important forensic implication of this finding, a study was conducted with volunteers receiving a single or repeated dosage of Myolastan®. Urine, hair and preserved oral fluid samples were analysed using a previously described sensitive and specific LC-MS-MS detection method allowing for the simultaneous quantification of tetrazepam, Diazepam, norDiazepam, oxazepam and temazepam. This study demonstrates that Diazepam can be observed in urine samples even after a single dose of Myolastan®. In addition, maintaining therapy for 1 week results in the detection of both Diazepam and norDiazepam in urine samples and of Diazepam in the first hair segment. Importantly, comparing urine and hair samples after a single intake of Diazepam versus the single and 1 week administration of Myolastan® shows that the possible metabolic conversion of tetrazepam to Diazepam is a more plausible explanation for the detection of Diazepam in biological samples after the intake of Myolastan®. As such, these results reveal that the presence of Diazepam and/or norDiazepam in biological samples from alleged drug-facilitated assault cases should be interpreted with care.