Pharmacokinetics of thiamine derivatives. II. Elimination of thiamine derivatives from the blood of rat.

Abstract

Some thiamine derivatives were compared pharmacokinetically about their elimination from blood after intravenous injection in rat. TPD (thiamine propyl disulfide), CCT (cyclocarbothiamine) and BTMP (S-benzoylthiamine monophosphate) were used as the typical thiamine derivatives. 1) It was found that the rates of conversion of TPD and CCT to thiamine in blood were rapid, but that of BTMP was slow. 2) TPD formed thiamine mainly through erythrocytes, but CCT formed thiamine mainly through plasma. 3) Volume of distribution (Vd or V1) of TPD, BTMP, CCT and thiamine were 37.6, 93.5, 187.5 and 256.1 ml, respectively. After intravenous injection of TPD, BTMP, CCT and thiamine rate constants of elimination of thiamine (keI or k'el) were 0.145, 0.151, 1.61 and 1.98 hr-1 respectively. Elimination constant of TPD was nearly equal to that of BTMP, and that of CCT to that of thiamine. 4) TPD and CCT behaved almost same in blood in vitro, except elimination of them from blood. 5) Since both TPD and BTMP were considerably taken up into erythrocytes, and also their elimination constants were equal to each other, the elimination constant must mean the constant of transfer rate from erythrocytes to plasma. 6) Pharmacokinetic model was proposed for each derivative.