Single and Multiple Dose PK–PD Characterization for Carisoprodol. Part I: Pharmacokinetics, Metabolites, and 2C19 Phenotype Influence. Double-Blind, Placebo-Controlled Clinical Trial in Healthy Volunteers

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Calvo, Aitana and Alonso, Saioa and Prieto, Esther and Ascaso del Rio, Ana and Ortuño, Jordi and Fernández, Nieves and Portolés Pérez, Antonio (2022) Single and Multiple Dose PK–PD Characterization for Carisoprodol. Part I: Pharmacokinetics, Metabolites, and 2C19 Phenotype Influence. Double-Blind, Placebo-Controlled Clinical Trial in Healthy Volunteers. Journal of Clinical Medicine, 11 (3). p. 858. ISSN 2077-0383

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Official URL: https://doi.org/10.3390/jcm11030858




Abstract

Carisoprodol was authorised in 1959 without a full pharmacokinetic–pharmacodynamic (PK–PD) characterisation. We designed a crossover, double-blind, placebo-controlled, randomized clinical trial to characterize the PKs of carisoprodol and its main active metabolite, meprobamate, after single (350 mg), multiple (350 mg/8 h, 14 days), and double (700 mg) doses of carisoprodol. Thirteen healthy volunteers were enrolled. After a single (350 mg) dose, the main carisoprodol parameters were (mean ± SD) Cmax: 2580 ± 1214 ng/mL, AUC0–∞: 8072 ± 6303 h·ng/mL, and half-life (T1/2): 2 ± 0.8 h. For meprobamate, the parameters were Cmax: 2181 ± 605 ng/mL and 34,529 ± 7747 h·ng/mL y 9 ± 1.9 h. Different profiles were found for extensive and poor 2C19 metabolizers. After 14 days of treatment (350 mg/8 h) the results for carisoprodol were (mean ± SD) Cmax: 2504 ± 730 ng/mL, AUC0–∞: 7451 ± 3615 h·ng/mL, and T1/2: 2 ± 0.7 h. For meprobamate (a steady state was reached), the parameters were Cmax: 5758 ± 1255 ng/mL and 79,699 ± 17,978 h·ng/mL y 8.7 ± 1.4 h. The study allowed for the full characterization of the pharmacokinetic profile of carisoprodol and meprobamate. Accumulation of meprobamate but not of carisoprodol was evident after 14 days of treatment.


Item Type:Article
Uncontrolled Keywords:carisoprodol; meprobamate; pharmacokinetics; phenotype; 2C19; clinical trial; drug abuse liability; central muscle relaxants
Subjects:Medical sciences > Medicine > Pharmacology
ID Code:72862
Deposited On:16 Jun 2022 14:47
Last Modified:17 Jun 2022 07:13

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