Single-dose pharmacokinetics and safety of iptakalim hydrochloride in Chinese healthy volunteers.
OBJECTIVE
To investigate the safety, pharmacokinetics and food effect of iptakalim in healthy adult Han Chinese volunteers.


METHODS
Study 1 was a randomized open-label, Latin square designed, single-dose, three-period, self-control crossover study. Six men and six women received 5, 10 and 20 mg of iptakalim orally. Study 2 was a randomized, open-label, single-dose, two-period, self-control crossover study. Ten men were included and each subject received 5 mg iptakalim orally, fasting and nonfasting.


RESULTS
No adverse effects were reported and no clinically meaningful changes in vital signs were found. Cmax, AUC(0-t) and AUC(0-∞) were proportional over the dose levels of 5, 10 and 20 mg. Tmax, t½ and CL/F were similarly independent of dose level. In the 5 mg and 20 mg group, the Cmax, AUC(0-t) and AUC(0-∞) in women were significantly higher than in men, although they showed no difference after correction by mg/kg doses in the 5 mg group. At the 5-mg dose level, no significant difference in pharmacokinetics was found in nonfasting and fasting subjects.


CONCLUSIONS
Single-dose pharmacokinetics of iptakalim showed dose proportionality over the dose levels of 5-20 mg. The pharmacokinetics showed gender differences in the 5 and 20 mg groups. Food had almost no impact on the pharmacokinetics at the 5 mg level.
Department of Clinical Pharmacology, PLA General Hospital, Tianjin, China.
Yun
Y
Cai
Dong
D
Chai
Fei
F
Pei
Yi
Y
Fang
Rui
R
Wang
Bei-Bei
BB
Liang
Wen-Yu
WY
Cui
Cun-Gang
CG
Bao
Hai
H
Wang
D000284:Administration, Oral; D000328:Adult; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D044466:Asian People; D001794:Blood Pressure / Q000187:drug effects; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D005215:Fasting / Q000378:metabolism; D005260:Female; D018565:Food-Drug Interactions; D006207:Half-Life; D006801:Humans; D054086:KATP Channels / Q000378:metabolism*; D008297:Male; D011437:Propylamines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D012737:Sex Factors; D055815:Young Adult
D000959:Antihypertensive Agents; D054086:KATP Channels; C502260:N-(1-methylethyl)-1,1,2-trimethylpropylamine; D011437:Propylamines