Pharmacokinetics and Comparative Bioavailability of Two Terbinafine Hydrochloride Formulations after Single-dose Administration in Chinese Healthy Subjects
15 December 2011 (online)
The bioavailability of a new terbinafine (CAS 91161-71-6) preparation was compared with a commercially available original preparation (reference) of the drug in 19 Chinese healthy male volunteers. The study was performed in an open, randomized, single blind two-sequence, two-period crossover design. Under fasting conditions, each subject received a single oral dose of 250 mg terbinafine as a test or reference formulation with a 7-day washout period between the two preparations. The plasma concentrations of terbinafine were analyzed by a sensitive liquid chromatography-ultraviolet spectrometry method. The pharmacokinetic parameters included AUC0-τ, AUC0-∞, Cmax, t1/2, and Tmax. The values of AUC0–t demonstrated nearly identical bioavailability of terbinafine from the examined formulations. The AUC0–48 of terbinafine was 5982.85 ± 2449.17 and 6761.63 ± 3140.33 ng · h/ml for the test and reference formulation, respectively. The maximum plasma concentration (Cmax) of terbinafine was 1656.25 ± 623.18 ng/ml for the test and 1552.07 ± 660.35 ng/ml for the reference product, respectively. No statistical differences were observed for Cmax and the area under the plasma concentrationtime curve for terbinafine. The 90% confidence limits calculated for Cmax and AUC from zero to infinity (AUC0–∞) of terbinafine were within the bioequivalence range (80%– 125% for AUC). This study shows that the test formulation is bioequivalent to the reference formulation of terbinafine.
- 1 Zehende H, Denouël J, Roy M, Le SchaubSaux P. Simultaneous determination of terbinafine (Lamisil) and five metabolites in human plasma and urine by high-performance liquid chromatography using on-line solid-phase extraction. J Chromatogr B. 1995; 664: 347-355
- 2 Denouël J, Keller HP, Schaub P, Delaborde C, Humbert H. Determination of terbinafine and its desmethyl metabolite in human plasma by high-performance liquid chromatography. J Chromatogr B. 1995; 663: 352-359
- 3 Lamisil-Clinical Pharmacology. http://www.rxlist.com/cgi/generic/terbin_cp.htm
- 4 Leyden JM. Pharmacokinetics and pharmacology of terbinafine and itraconazole. J Am Acad Dermatol. 1998; 38: S42-47
- 5 US Department of Health and Human Services. Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Guidance for Industry, Bioanalytical Method Validation. 2001.
- 6 Almeida S, Filipe A, Vallée F, Tanguay M, Larouche R, Lainesse A. Comparative bioavailability of two formulations of terbinafine. Data from a cross-over, randomised, open-label bioequivalence study in healthy volunteers. Arzneimittel-Forschung (Drug Research). 2004; 54: 757-762