Pharmacokinetic studies on the extended-release tablets of lovastatin in human volunteers

Aim: To study the pharmacokinetics of lovastatin after a single and multiple oral doses of extended-release lovastatin tablets in 20 healthy Chinese volunteers by LC-MS/MS. Methods: Lovasatatin is quantitatively determined by LC-MS/MS using positive ion detection with selected reaction monitoring (SRM). Extended-release or convention tablets were given to 20 healthy volunteers single dose(40 mg) or multiple doses (20 mg × 6) in a two-way crossover design. Blood was drawn at different intervals after treatment. Results: The LC-MS/MS method was proved to be linear over the range of 0.05-10.0 ng/mL of lovastatin with limit of quantitation of 0.05 ng/mL. Compared with conventional tablet, the relative bioavailability of lovastatin ER is about (148.5 ± 43.1) % and (140.7 ± 32.8) % after single or multiple doses, respectively. The pharmacokinetic parameters of lovastatin after single dose were as follows: MRT were (14.61 ± 7.27) h and (29.72 ± 17.22)h, t_max were (4.2 ± 2.1)h and (12.3 ± 7.5) h, c_max were (1.98 ± 1.01) ng/mL and 1.64 ± 0.62) ng/mL, and t_1/2 were (12.16 ± 5.18) h and (18.17 ± 10.78) h for conventional tablet and lovastatin ER, respectively. The mean steady state concentrations (c_ss) of lovastatin after six consecutive days treatment with the two formulations were (0.57 ± 0.27) and (0.80 ± 0.43) ng/mL with fluctuate degree (DF) of 2.64 ± 1.10 and 0.97 ± 0.36, respectively. Conclusions: Compared with the conventional tablet, the lovastatin ER shown a delayed t_max, lower c_max and higher bioavailability.