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- Title
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.
- Authors
Calvo, Aitana; Alonso, Saioa; Prieto, Esther; Ascaso-del-Rio, Ana; Ortuño, Jordi; Fernandez, Nieves; Portolés, Antonio
- 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.
- Subjects
CLINICAL trials; PHARMACOKINETICS; VOLUNTEERS; PHENOTYPES; METABOLITES
- Publication
Journal of Clinical Medicine, 2022, Vol 11, Issue 3, p858
- ISSN
2077-0383
- Publication type
Article
- DOI
10.3390/jcm11030858