Multiple dose pharmacokinetics of four different doses of nisoldipine in hypertensive patients.
This randomized double-blind parallel group study characterized the pharmacokinetics of the calcium channel antagonist, nisoldipine (core-coat tablets), administered once daily for 7 days in doses of 5 mg (n = 12), 10 mg (n = 13), 20 mg (n = 12), and 30 mg (n = 11) to patients with mild to moderate hypertension. Serial blood samples were obtained from 0 to 24 hours and from 0 to 48 hours after nisoldipine administration on days 1 and 7, respectively. Nisoldipine plasma concentrations were determined by gas chromatography with electron capture detection. No statistically significant difference was found in dose-normalized area under the curve between the four groups. Area under the curve (standardized to body weight) correlated to dose (r = .74, P less than .05). No significant difference existed in oral clearance (L/h/kg) when analyzed for equivalence across the four doses: 8.21 +/- 3.47 (5 mg), 11.84 +/- 13.85 (10 mg), 11.48 +/- 7.49 (20 mg), and 10.36 +/- 5.49 (30 mg). The present investigation characterizes the pharmacokinetics of nisoldipine core-coat tablets in hypertensive patients and demonstrates the dose proportionality or linearity of nisoldipine plasma concentrations and area under the curve, measured over a dose range of 5 to 30 mg.
Chandler
M H
MH
Drug Product Evaluation Unit, University of Kentucky Medical Center, Lexington.
Clifton
G D
GD
Lettieri
J T
JT
Mazzu
A L
AL
Allington
D R
DR
Thieneman
A C
AC
Foster
T S
TS
Harrison
M R
MR
D000328:Adult; D000368:Aged; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D015737:Nisoldipine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D013607:Tablets
D003692:Delayed-Action Preparations; D013607:Tablets; D015737:Nisoldipine