Transl Clin Pharmacol.  2017 Mar;25(1):10-14. 10.12793/tcp.2017.25.1.10.

Comparative pharmacokinetic and tolerability evaluation of two simvastatin 20 mg formulations in healthy Korean male volunteers

• Moon SJ
• Lee S
• Jang K
• Yu KS
• Yim SV
• Kim BH

• KMID: 2411413
• DOI: http://doi.org/10.12793/tcp.2017.25.1.10

Abstract

Simvastatin is used to reduce plasma cholesterol by inhibiting 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and is primarily used to treat hypercholesterolemia. This study was conducted to assess the bioequivalence between the generic formulation of simvastatin 20 mg and the branded formulation of simvastatin 20 mg. A generic formulation of simvastatin 20 mg tablet was developed and the pharmacokinetics of the generic formulation were compared with those of the branded formulation of simvastatin 20 mg tablet in 33 healthy male volunteers after a single oral dose in a randomized, open-label, two-period, two-sequence, crossover study. The reference (Zocor®, MSD Korea LTD.) and test (Simvarotin®, Korea Arlico Pharm Co., Ltd.) formulations, two 20 mg tablets each, were administered to all subjects in fasting status. The serial blood samples for pharmacokinetic analysis were collected before dosing and up to 24 hours post-dose, and plasma concentrations of simvastatin were determined by liquid chromatography-tandem mass spectrometry. The pharmacokinetic parameters including T(max), C(max), AUC(last), AUC(inf) and t½ were calculated for both formulations by non-compartmental method, and the log-transformed C(max) and AUC(last) were compared statistically. Geometric mean ratios (90% confidence intervals) of the test to the reference formulation in C(max) and AUC(last) were 0.9652 (0.8302-1.1223) and 0.9891 (0.8541-1.1455), respectively. No significant differences in tolerability profiles were noted between the two formulations. The two formulations of simvastatin 20 mg tablets exhibited comparable pharmacokinetic profiles and 90% confidence intervals were within the acceptable range of bioequivalence criteria.

Keyword

Simvastatin; Pharmacokinetics; Bioequivalence

MeSH Terms

Cholesterol
Coenzyme A
Cross-Over Studies
Fasting
Humans
Hypercholesterolemia
Korea
Male*
Mass Spectrometry
Methods
Oxidoreductases
Pharmacokinetics
Plasma
Simvastatin*
Tablets
Therapeutic Equivalency
Volunteers*
Cholesterol
Coenzyme A
Oxidoreductases
Simvastatin
Tablets

Figure

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  Figure 1 Mean plasma simvastatin concentration versus time profile of the reference and test formulations after a single oral administration of simvastatin 40 mg (20 mg × 2 tablets) in linear (left) and semi-logarithmic (right) scale.

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  Figure 2 Individual plasma simvastatin concentration versus time profile of the reference (upper) and test formulations (lower) after a single oral administration in linear scale.

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  Figure 3 Comparison of the individual Cmax (upper) and AUClast (lower) between the reference and test formulations after a single oral administration.

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