Concise total syntheses of phelligridins A, C, and D.

We have established a concise and scalable synthetic pathway for phelligridins A (1), C (2) and D (3). The synthetic highlights were Suzuki-Miyaura coupling and aldol-type condensation of α-pyrone. Phelligridin A was synthesized in four steps, while phelligridins C and D were each synthesized in six steps.

Effect of meropenem on disposition kinetics of valproate and its metabolites in rabbits.

Purpose: We investigated the effect of meropenem (MEPM) on the disposition kinetics of valproate (VPA) and its metabolites in rabbits.

Methods: Rabbits were given 75 mg/kg VPA intravenously with or without 300 mg/kg MEPM.

Results: The plamsa total clearance of VPA was significantly increased to about 1.

Kinetic phenotypic diagnosis of N-acetylation polymorphism in patients based on ratio of urinary metabolites of salicylazosulfapyridine.

We found that N-acetylation polymorphism can be evaluated from the disposition kinetics of sulfapyridine (SP) and 5-aminosalicylic acid (5-ASA) and their acetylated metabolites generated by N-acetyltransferase (NAT2) after oral administration of salicylazosulfapyridine (SASP). In 126 Japanese subjects, the homozygote of NAT2*4 was the most frequent (40%), followed by heterozygotes of NAT2*4 and mutant genes (28% NAT2*4/*6A, 15% NAT2*4/*7B, and 2% NAT2*4/*5B). Combinations of mutant genes accounted for 16%.

[Studies on the mechanism of subcellular distribution of basic drugs based on their lipophilicity].

This paper described the studies on the mechanism of subcellular distribution of lipophilic weak bases. Although the tissue distribution of basic drugs appeared to decrease with time simply in parallel with their plasma concentration, their subcellular distribution in various tissues exhibited a variety of patterns. Basic drugs were distributed widely in various tissues, but were concentrated in lung granule fraction, where their accumulation was dependent on their lipophilicity and lysosomal uptake.