John S Markowitz, Ludmila De Faria, Qingchen Zhang, Philip W Melchert, Reginald F Frye, Brandon O Klee, Yuli Qian
{"title":"大麻二酚对健康人哌醋甲酯药动学的影响。","authors":"John S Markowitz, Ludmila De Faria, Qingchen Zhang, Philip W Melchert, Reginald F Frye, Brandon O Klee, Yuli Qian","doi":"10.1159/000527189","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Cannabidiol (CBD) is a widely utilized nonpsychoactive cannabinoid available as an over-the-counter supplement, a component of medical cannabis, and a prescriptive treatment of childhood epilepsies. In vitro studies suggest CBD may inhibit a number of drug-metabolizing enzymes, including carboxylesterase 1 (CES1). The aim of this study was to evaluate effect of CBD on the disposition of the CES1 substrate methylphenidate (MPH).</p><p><strong>Methods: </strong>In a randomized, placebo-controlled, crossover study, 12 subjects ingested 750 mg of CBD solution, or alternatively, a placebo solution twice daily for a 3-day run-in period followed by an additional CBD dose (or placebo) and a single 10 mg dose of MPH and completed serial blood sampling for pharmacokinetic analysis. MPH and CBD concentrations were measured by liquid chromatography with tandem mass spectrometry.</p><p><strong>Results: </strong>The C<sub>max</sub> (mean ± CV) for the CBD group and placebo group was 13.5 ± 43.7% ng/mL and 12.2 ± 36.4% ng/mL, respectively. AUC<sub>inf</sub> (ng/mL*h) for the CBD group and placebo group was 70.7 ± 32.5% and 63.6 ± 25.4%, respectively. The CBD AUC<sub>0-8h</sub> (mean ± CV) was 1,542.2 ± 32% ng/mL*h, and C<sub>max</sub> was 389.2 ± 39% ng/mL. When compared to MPH only, the geometric mean ratio (CBD/control, 90% CI) for AUC<sub>inf</sub> and C<sub>max</sub> with CBD co-administration was 1.09 (0.89, 1.32) and 1.08 (0.85, 1.37), respectively.</p><p><strong>Discussion/conclusion: </strong>Although the upper bound of bioequivalence was not met, the mean estimates of AUC and C<sub>max</sub> ratios were generally small and unlikely to be of clinical significance.</p>","PeriodicalId":18415,"journal":{"name":"Medical Cannabis and Cannabinoids","volume":" ","pages":"199-206"},"PeriodicalIF":0.0000,"publicationDate":"2022-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c5/6e/mca-0005-0199.PMC9710314.pdf","citationCount":"3","resultStr":"{\"title\":\"The Influence of Cannabidiol on the Pharmacokinetics of Methylphenidate in Healthy Subjects.\",\"authors\":\"John S Markowitz, Ludmila De Faria, Qingchen Zhang, Philip W Melchert, Reginald F Frye, Brandon O Klee, Yuli Qian\",\"doi\":\"10.1159/000527189\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>Cannabidiol (CBD) is a widely utilized nonpsychoactive cannabinoid available as an over-the-counter supplement, a component of medical cannabis, and a prescriptive treatment of childhood epilepsies. In vitro studies suggest CBD may inhibit a number of drug-metabolizing enzymes, including carboxylesterase 1 (CES1). The aim of this study was to evaluate effect of CBD on the disposition of the CES1 substrate methylphenidate (MPH).</p><p><strong>Methods: </strong>In a randomized, placebo-controlled, crossover study, 12 subjects ingested 750 mg of CBD solution, or alternatively, a placebo solution twice daily for a 3-day run-in period followed by an additional CBD dose (or placebo) and a single 10 mg dose of MPH and completed serial blood sampling for pharmacokinetic analysis. MPH and CBD concentrations were measured by liquid chromatography with tandem mass spectrometry.</p><p><strong>Results: </strong>The C<sub>max</sub> (mean ± CV) for the CBD group and placebo group was 13.5 ± 43.7% ng/mL and 12.2 ± 36.4% ng/mL, respectively. AUC<sub>inf</sub> (ng/mL*h) for the CBD group and placebo group was 70.7 ± 32.5% and 63.6 ± 25.4%, respectively. The CBD AUC<sub>0-8h</sub> (mean ± CV) was 1,542.2 ± 32% ng/mL*h, and C<sub>max</sub> was 389.2 ± 39% ng/mL. When compared to MPH only, the geometric mean ratio (CBD/control, 90% CI) for AUC<sub>inf</sub> and C<sub>max</sub> with CBD co-administration was 1.09 (0.89, 1.32) and 1.08 (0.85, 1.37), respectively.</p><p><strong>Discussion/conclusion: </strong>Although the upper bound of bioequivalence was not met, the mean estimates of AUC and C<sub>max</sub> ratios were generally small and unlikely to be of clinical significance.</p>\",\"PeriodicalId\":18415,\"journal\":{\"name\":\"Medical Cannabis and Cannabinoids\",\"volume\":\" \",\"pages\":\"199-206\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2022-11-04\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c5/6e/mca-0005-0199.PMC9710314.pdf\",\"citationCount\":\"3\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Medical Cannabis and Cannabinoids\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1159/000527189\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2022/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q1\",\"JCRName\":\"Medicine\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Medical Cannabis and Cannabinoids","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1159/000527189","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2022/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"Medicine","Score":null,"Total":0}
The Influence of Cannabidiol on the Pharmacokinetics of Methylphenidate in Healthy Subjects.
Introduction: Cannabidiol (CBD) is a widely utilized nonpsychoactive cannabinoid available as an over-the-counter supplement, a component of medical cannabis, and a prescriptive treatment of childhood epilepsies. In vitro studies suggest CBD may inhibit a number of drug-metabolizing enzymes, including carboxylesterase 1 (CES1). The aim of this study was to evaluate effect of CBD on the disposition of the CES1 substrate methylphenidate (MPH).
Methods: In a randomized, placebo-controlled, crossover study, 12 subjects ingested 750 mg of CBD solution, or alternatively, a placebo solution twice daily for a 3-day run-in period followed by an additional CBD dose (or placebo) and a single 10 mg dose of MPH and completed serial blood sampling for pharmacokinetic analysis. MPH and CBD concentrations were measured by liquid chromatography with tandem mass spectrometry.
Results: The Cmax (mean ± CV) for the CBD group and placebo group was 13.5 ± 43.7% ng/mL and 12.2 ± 36.4% ng/mL, respectively. AUCinf (ng/mL*h) for the CBD group and placebo group was 70.7 ± 32.5% and 63.6 ± 25.4%, respectively. The CBD AUC0-8h (mean ± CV) was 1,542.2 ± 32% ng/mL*h, and Cmax was 389.2 ± 39% ng/mL. When compared to MPH only, the geometric mean ratio (CBD/control, 90% CI) for AUCinf and Cmax with CBD co-administration was 1.09 (0.89, 1.32) and 1.08 (0.85, 1.37), respectively.
Discussion/conclusion: Although the upper bound of bioequivalence was not met, the mean estimates of AUC and Cmax ratios were generally small and unlikely to be of clinical significance.
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