Effect of steady-state atorvastatin on the pharmacokinetics of a single dose of colchicine in healthy adults under fasted conditions.
OBJECTIVE
Colchicine is commonly prescribed for gout. While minimally metabolized by the cytochrome P450 (CYP) 3A4 isoenzyme, colchicine is a substrate for P-glycoprotein (P-gp). Atorvastatin is metabolized primarily by CYP3A4 and is a P-gp inhibitor. Patients with gout often have dyslipidemia; therefore, the potential for co-administration of atorvastatin and colchicine exists. The objective of this study was to determine the effect of oral atorvastatin on the pharmacokinetics of a single, oral dose of colchicine.


METHODS
Twenty-four healthy adult subjects were enrolled in this single-center, open-label, non-randomized, one-sequence, two-period drug-drug interaction study. On day 1, subjects received a single oral dose of colchicine 0.6 mg. After a 14-day washout, subjects received atorvastatin 40 mg once daily for 14 days followed by a single dose of colchicine 0.6 mg co-administered with atorvastatin 40 mg on day 28. Main outcome measures were colchicine maximum plasma concentration (C max), area under the plasma concentration-time curve (AUC) from time zero to the last measurable concentration (AUC last), and AUC from time zero to infinity (AUC∞), which were compared with and without concurrent atorvastatin.


RESULTS
Colchicine AUC last, AUC∞, and C max increased by 27, 24, and 31 %, respectively, when co-administered with atorvastatin. Corresponding 90 % confidence intervals around the ratios were outside the established no-effect 80-125 % interval.


CONCLUSIONS
Increased colchicine exposure was observed after a single dose of colchicine was administered with steady-state atorvastatin. Additional studies with multiple dosing of both drugs are needed to further determine the clinical implications of these results.
Clinical Operations & Development Sun Pharma USA, 270 Prospect Plains Road, Cranbury, NJ, 08512, USA, matthew.davis@sunpharmausa.com.
Matthew W
MW
Davis
Suman
S
Wason
D000328:Adult; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D019540:Area Under Curve; D000069059:Atorvastatin; D003078:Colchicine / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D004347:Drug Interactions; D005215:Fasting; D005260:Female; D006074:Gout Suppressants / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D064368:Healthy Volunteers; D006538:Heptanoic Acids / Q000009:adverse effects / Q000494:pharmacology*; D006801:Humans; D008297:Male; D011758:Pyrroles / Q000009:adverse effects / Q000494:pharmacology*; D055815:Young Adult
D000924:Anticholesteremic Agents; D006074:Gout Suppressants; D006538:Heptanoic Acids; D011758:Pyrroles; D000069059:Atorvastatin; D003078:Colchicine