Zolpidem Pharmacokinetic Properties in Young Females: Influence of Smoking and Oral Contraceptive Use

Olubodun, J.; Ochs, Hermann R.; Trüten, V.; Klein, A.; Moltke, Lisa L. von; Harmatz, Jerold S.; Shader, Richard I.; Greenblatt, David J.

doi:10.1177/009127002401382623

Cited by 20 publications

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“…Values of zolpidem t ½ and clearance are consistent with prior pharmacokinetic studies [17][18][19][41][42][43]50,51 and did not differ between IR and MR. Values of zolpidem t ½ and clearance are consistent with prior pharmacokinetic studies [17][18][19][41][42][43]50,51 and did not differ between IR and MR.…”

Section: Greenblatt Et Alsupporting

confidence: 84%

Dynamics and Kinetics of a Modified‐Release Formulation of Zolpidem: Comparison With Immediate‐Release Standard Zolpidem and Placebo

Greenblatt

Legangneux

Harmatz

et al. 2006

The Journal of Clinical Pharma

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Modified-release (MR) zolpidem was developed to maintain effective plasma concentrations during the 3- to 6-hour post-dosage interval, corresponding to the middle portion of the typical sleep interval. Modified-release zolpidem (12.5 mg), standard immediate-release (IR) zolpidem (10 mg), and placebo were compared in a double-blind, single-dose, 3-way crossover daytime study of healthy volunteers (n = 70 completers). Effect areas for electroencephalographic beta amplitude during 0 to 8 hours and 3 to 6 hours after dosage were greater for MR compared to IR (P < .001). The digit-symbol substitution test and sedation rating scales behaved similarly. MR and IR did not differ in effects at 8 hours post-dosage nor in halflife or clearance. Time of peak plasma concentration (tmax) was significantly longer for MR (2.4 vs 2.0 hours, P < .004), and dose-normalized peak plasma concentration (Cmax) was lower (12.2 vs 14.0 ng/mL/mg, P < .001). MR zolpidem also had greater area under the plasma concentration curve (AUC) during the 3- to 6-hour interval (P < .001). Thus, MR zolpidem produces sustained plasma levels compared to IR, with resulting enhancement of pharmacodynamic effects in the 3- to 6-hour post-dosage interval.

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Section: Greenblatt Et Alsupporting

confidence: 84%

Dynamics and Kinetics of a Modified‐Release Formulation of Zolpidem: Comparison With Immediate‐Release Standard Zolpidem and Placebo

Greenblatt

Legangneux

Harmatz

et al. 2006

The Journal of Clinical Pharma

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“…59,61,62 External factors such as consumption of alcohol, alcohol-induced liver disease, smoking, use of contraceptive steroids, pregnancy, and concomitant use of other drugs might influence C max or C ss under some circumstances. [85][86][87][88] Pharmaceutical aspects such as the dosage form, whether tablet, syrup, or sustained-release product, as well as route of administration can have a large impact on C max for the same dose of drug administered. Analytic considerations, particularly the condition of the specimen and the type of matrix, whether plasma, serum, or whole blood, are clearly important considerations owing to uneven distribution of drugs between plasma and red cells.…”

Section: Discussionmentioning

confidence: 99%

Concentrations of Scheduled Prescription Drugs in Blood of Impaired Drivers: Considerations for Interpreting the Results

Jones

Holmgren

Kugelberg

2007

Therapeutic Drug Monitoring

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We report the concentrations of scheduled prescription drugs in blood samples from people arrested in Sweden for driving under the influence of drugs (DUID). The investigation covered a 2 year period 2004 (N = 7052 cases) and 2005 (N = 7759 cases) and was prompted by recent legislation stipulating zero-concentration limits in blood for controlled substances. However, prescription drugs are exempt from the zero-limit law provided that the medication was being used in accordance with a doctor's prescription. The blood concentrations of various psychoactive substances were compared with the limits of quantitation of the analytic method used and the so-called therapeutic concentration range according to various reference books and tabulations. Diazepam [N = 1950 (26%)] and nordazepam [N = 2168 (28%)] were the therapeutic agents most frequently identified in these forensic blood samples along with other benzodiazepines such as alprazolam [N = 430 (5.6%)], flunitrazepam [N = 308 (4.0%)], and nitrazepam [N = 222 (2.9%)]. The newer hypnotics, exemplified by zolpidem [N = 148 (1.9%)] and zopiclone [N = 111 (1.5%)], were also high on the list of psychoactive substances identified. Interpreting the concentration of a prescription drug in blood in relation to whether the person had taken an overdose or was abusing the substance in question is not always easy. The age, gender, degree of obesity, and ethnicity of the person concerned; the pharmacokinetic profile of the drug; polymorphism of drug-metabolizing enzymes as well as liver and kidney function and blood hematocrit need to be considered. Among preanalytic factors, stability of the drug in blood after sampling, the type of tubes and preservatives used, the dosage form and route of administration deserve consideration. When therapeutic drug monitoring concentrations are compared with forensic toxicology results, then the plasma-to-whole blood distribution ratio of the drug also needs to be considered. In blood samples from DUID suspects, the concentrations of many commonly used sedatives and hypnotics exceeded the accepted therapeutic limits, which gives an indication of the abuse potential of these types of medications.

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“…Zaleplon has few significant interactions due to its main metabolic pathway being aldehyde oxidase. Smoking and oral contraceptive use have been studied in young women, with little effect on zolpidem kinetics [28]. The combination of zolpidem and benzodiazepines has been shown to significantly increase the risk of hospitalization and hip fractures in the elderly [29].…”

Section: Pharmacokineticsmentioning

confidence: 99%

The Clinical and Forensic Toxicology of Z-drugs

Gunja

2013

J. Med. Toxicol.

151

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The Z-drugs zolpidem, zopiclone, and zaleplon were hailed as the innovative hypnotics of the new millennium, an improvement to traditional benzodiazepines in the management of insomnia. Increasing reports of adverse events including bizarre behavior and falls in the elderly have prompted calls for caution and regulation. Z-drugs have significant hypnotic effects by reducing sleep latency and improving sleep quality, though duration of sleep may not be significantly increased. Z-drugs exert their effects through increased γ-aminobutyric acid (GABA) transmission at the same GABA-type A receptor as benzodiazepines. Their pharmacokinetics approach those of the ideal hypnotic with rapid onset within 30 min and short half-life (1-7 h). Zopiclone with the longest duration of action has the greatest residual effect, similar to short-acting benzodiazepines. Neuropsychiatric adverse events have been reported with zolpidem including hallucinations, amnesia, and parasomnia. Poisoning with Z-drugs involves predominantly sedation and coma with supportive management being adequate in the majority. Flumazenil has been reported to reverse sedation from all three Z-drugs. Deaths from Z-drugs are rare and more likely to occur with polydrug overdose. Zdrugs can be detected in blood, urine, oral fluid, and postmortem specimens, predominantly with liquid chromatography-mass spectrometry techniques. Zolpidem and zaleplon exhibit significant postmortem redistribution. Zaleplon with its ultra-short half-life has been detected in few clinical or forensic cases possibly due to assay unavailability, low frequency of use, and short window of detection. Though Z-drugs have improved pharmacokinetic profiles, their adverse effects, neuropsychiatric sequelae, and incidence of poisoning and death may prove to be similar to older hypnotics.

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Zolpidem Pharmacokinetic Properties in Young Females: Influence of Smoking and Oral Contraceptive Use

Cited by 20 publications

References 0 publications

Dynamics and Kinetics of a Modified‐Release Formulation of Zolpidem: Comparison With Immediate‐Release Standard Zolpidem and Placebo

Dynamics and Kinetics of a Modified‐Release Formulation of Zolpidem: Comparison With Immediate‐Release Standard Zolpidem and Placebo

Concentrations of Scheduled Prescription Drugs in Blood of Impaired Drivers: Considerations for Interpreting the Results

The Clinical and Forensic Toxicology of Z-drugs

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