One year administration of almitrine bismesylate (Vectarion) to chronic obstructive pulmonary disease patients: pharmacokinetic analysis.
A double blind study utilizing orally administered almitrine bismesylate was conducted involving 36 stable chronic obstructive pulmonary disease (COPD) patients with hypoxia and with and without hypercapnia. The patients received 50 mg tablets twice daily for 360 days. Blood samples were taken both at predose and 3 hours postdose at different periods throughout 1 year dosage regimen and plasma levels were analyzed by a GLC method using a nitrogen-phosphorous detector. Plasma almitrine concentrations indicate large variability at each time sample. Results suggest an increasing trend in the almitrine plasma levels as a function of time. Plasma almitrine levels increased significantly (p less than 0.01) between test day 14 and test day 360 (243 +/- 213 per cent and 199 +/- 170 per cent for predose and 3h postdose samples, respectively) indicating that steady state is not achieved by day 14. Almitrine plasma levels appear to stabilize between test day 90 and test day 180. The effective multiple dose half-life for almitrine bismesylate in plasma is estimated to be 32 days. About half of the patients exhibited steady state peak plasma almitrine levels above 500 ng ml-1. In addition, 19 per cent of the patients achieved maximum apparent steady state almitrine levels greater than 700 ng ml-1. Mean accumulation was estimated to be 4.21 +/- 1.98 at one year.
Stavchansky
S
S
College of Pharmacy, Division of Pharmaceutics, University of Texas, Austin 78712.
Doluisio
J T
JT
Macleod
C M
CM
Szalkowski
M B
MB
Bachand
R T
RT
Heilman
R
R
Sebree
T B
TB
Geary
R S
RS
D015765:Almitrine; D000697:Central Nervous System Stimulants / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006207:Half-Life; D006801:Humans; D008173:Lung Diseases, Obstructive / Q000188:drug therapy / Q000378:metabolism*; D010879:Piperazines / Q000493:pharmacokinetics* / Q000627:therapeutic use; D013997:Time Factors
D000697:Central Nervous System Stimulants; D010879:Piperazines; D015765:Almitrine