Single oral dose proportionality pharmacokinetics of almitrine bismesylate in humans

✍ Scribed by S. Stavchansky; J. T. Doluisio; C. M. MacLeod; M. B. Szalkowski; R. T. Bachand Jr.; R. Heilman; T. B. Sebree; R. S. Geary

• Publisher: John Wiley and Sons
• Year: 1989
• Tongue: English
• Weight: 414 KB
• Volume: 10
• Category: Article
• ISSN: 0142-2782
• DOI: 10.1002/bdd.2510100302

✦ Synopsis

A single-blind study was conducted in 10 healthy male subjects. Each subject was tested with four single oral doses of capsules containing 25, 50, 100, 200mg almitrine bismesylate and one dose of placebo. Blood samples were drawn as a function of time and the concentration of almitrine in plasma was determined by gas chromatography utilizing nitrogen-phosphorus detection. Linear regression analysis of the data suggested that a deviation from linearity existed between the area under the plasma concentration time curves and the dose ( R = 0-96). Linear analysis of the individual data indicates that a slight negative deviation from linearity is apparent for the 200mg dose. The same trend was observed for the mean maximum almitrine plasma concentration, C,,, which ranged from 38.9 f 11.8 to 286.2 f 99.1 ngml-' for the 25 and 200 mg dose, respectively. The time to peak was relatively constant regardless of the administered dose and ranged from 2.4 i 0.5 h to 2.8 f 0-8 h. Good agreement was obtained between the observed bioavailability parameters and those predicted from the nonlinear fit of the data. Further kinetic analysis of the data revealed mean total body clearance over fraction of dose absorbed ranging from 268.2 f 132.8 to 436.4 f 191.4 ml min-' for doses 50 and 200mg, respectively. KEY WORDS Almitrine bismesylate Bioavailability parameters Dose linearity INTRODUCTION Almitrine bismesylate,* also known as S-2620 and 2,4 [bis(allylamino)-6-[4 bi @-fluorophenyl)methyl]-1-piperazinyl]-s-triazine bismesylate, is a new and novel drug demonstrated to be safe and efficacious in relieving the hypoxemia and *Vectarion@, manufactured by Servier Laboratories in France.