The oral single-dose pharmacokinetics and bioavailability of mefloquine (M) in combination with pyrimethamine (P) and sulfadoxine (S) from a single non-lacquered tablet (NL; M 250 mg, P 25 mg, S 500 mg) and two lacquered tablets (L; M 125 mg, P 12.5 mg, S 250 mg) were investigated in 6 healthy Chinese volunteers. The plasma concentrations of P and S were measured by high-performance liquid chromatography with UV detector over 11 days and the plasma concentrations of M were measured by gas chromatography with electron capture for 63 days. The pharmacokinetic evaluation of each of the three components was based on the assumption of an open linear one-compartment model. The model-independent pharmacokinetic parameters such as elimination half-life and total clearance of P and S in the present study were not appreciably different from those reported previously. The pharmacokinetic parameters of elimination half-life, total clearance and apparent volume of distribution of M were 11 days, 45.8 ml/h kg, and 14.8 1/kg, respectively. Compared to previously published data on M in Thai patients, Caucasian, Brazilian and African subjects, it was found that the elimination half-life in Chinese subjects was similar to that in Thai patients, but different from Caucasian, Brazilian and African subjects. There were significant differences in total clearance and volume of distribution among Chinese subjects and Thai patients. The differences in pharmacokinetic behaviour of M between subject groups needs to be examined further. The relative bioavailability of P, S, and M in the lacquered and non-lacquered tablet formulations in the 6 subjects studied were not significantly different with values (mean ± SD) of 0.98 ± 0.06,1.28 ± 0.20 and 1.02 ± 0.17, respectively. The combination of mefloquine (M) with pyrimethamine (P) and sulfadoxine (S; Fansimef) is an effective antimalarial in adults and children [1–3]. P and S inhibit two different enzymes (dihydrofolate reductase and dihydropterate synthetase) in the plasmodial folate biosynthesis pathway and the synergistic action of these drugs is enhanced by the additive effect of M, a quinoline methanol derivative [4]. The triple combination also delays the development of resistance [5] and in vitro studies confirm this efficacy even when there is a P-S resistance [6]. The pharmacokinetics of M in combination with P and S have been described in Brazilian [7], African [8], Caucasian [8, 9], and Thai patients [10] and Thai volunteers [11]. The present study investigates the pharmacokinetics of M in combination with P and S and the bioavailability of these drugs from non-lacquered and lacquered tablets in a cross-over design in 6 Chinese male volunteers.

This study investigates the effect of epigallocatechin-3-gallate (EGCG), a major ingredient of green tea, on the pharmacokinetics of amlodipine in rats. The pharmacokinetics of orally administered amlodipine (1 mg/kg) with or without EGCG pretreatment (30 mg/kg/day for 10 days) were investigated. Plasma concentrations of amlodipine were determined by using a sensitive and reliable liquid chromatography with tandem mass spectroscopy (LC-MS/MS) method. The effects of EGCG on the metabolic stability of amlodipine were investigated by using rat liver microsome incubation systems. The results indicated that when the rats were pretreated with EGCG, the C of amlodipine increased from 16.32 ± 2.57 to 21.44 ± 3.56 ng/mL (p < 0.05), the T decreased from 5.98 ± 1.25 to 4.01 ± 1.02 h (p < 0.05), and the AUC increased from 258.12 ± 76.25 to 383.34 ± 86.95 μg h L (p < 0.05), which suggested that the pharmacokinetic behavior of amlodipine was affected after oral co-administration of EGCG. Additionally, the metabolic half-life was prolonged from 31.3 ± 5.6 to 52.6 ± 7.9 min (p < 0.05) with the pretreatment of EGCG. It can be speculated that the drug-drug interaction between EGCG and amlodipine might occur, which might have resulted from the metabolism inhibition of amlodipine by EGCG when they were co-administered.

Context: Danshen tablets (DST), an effective traditional Chinese multi-herbal formula, are often combined with amlodipine (ALDP) for treating coronary heart disease. Objective: This study investigated the effects of DST on the pharmacokinetics of ALDP and the potential mechanism. Materials and methods: The pharmacokinetics of ALDP (1 mg/kg) in male Sprague–Dawley rats ( n = 6), with or without pretreatment of DST (100 mg/kg for 7 d), were investigated using LC-MS/MS. The effects of DST on the metabolic stability of ALDP were also investigated using rat liver microsomes (RLM). Results: The results indicated that C max (16.25 ± 2.65 vs. 22.79 ± 2.35 ng/ml), AUC (0– t ) (222.87 ± 59.95 vs. 468.32 ± 69.87 n gh/ml), and t 1/2 (10.60 ± 1.05 vs. 14.15 ± 1.59 h) decreased significantly when DST and ALDP were co-administered, which suggested that DST might influence the pharmacokinetic behaviour of ALDP when they are co-administered. The metabolic stability of ALDP was also decreased (23.6 ± 4.7 vs. 38.9 ± 5.2) with the pretreatment of DST. Discussion and conclusions: This study indicated that DST could accelerate the metabolism of ALDP in RLM and change the pharmacokinetic behaviours of ALDP. Accordingly, these results showed that the herb–drug interaction between DST and ALDP might occur when they were co-administered. Therefore, the clinical dose of ALDP should be increased when DST and ALDP are co-administered.

Abstract

As the third-generation supramolecular main structure, calixarenes, especially chiral calixarenes, have been applied to various fields. In this study, the bridging chiral de-tert-butylcalix[4]arene derivatives with an amide group attached to a chiral point was synthesized for the first time, which provided a new group for its structural derivation at the bridging chiral position. The racemic compound 2 was optically resolved by column chromatography on silica gel with the aid of the chiral auxiliary (1S)-(+)-10-camphorsulfonyl chloride, and finally a pair of optically pure bridging chiral de-tert-butylcalix[4]arene derivatives 4a and 4b were obtained. The results of experimental and calculated ECD showed that compounds 4a and 4b were a pair of enantiomers, and their absolute configurations were designated S and R, respectively. This study provides new idea for the derivatization of specific chiral groups based on bridging chiral calix[4]arenes and their chiral resolution.