Single dose pharmacokinetics of manidipine in hepatic impaired patients and healthy controls.
The pharmacokinetics and safety of a single oral dose of 20 mg manidipine dihydrochloride have been studied in 8 patients with mild to moderate hepatic impairment (grade A or B in Child's classification, or score < or = 7 in Pugh's modification of Child's classification), and in 12 healthy subjects. They received one 20 mg manidipine dihydrochloride tablet with 100 ml of tap water after a standard breakfast. Manidipine was determined using HPLC with electrochemical detection from plasma samples taken up to 24 or 36 h after dosing. The medication was well tolerated. A trend toward higher Cmax, AUC, and MRT was observed in patients with a more severe hepatic impairment, as a consequence of reduction in the liver metabolic function. Patients with grade A hepatic impairment did not exhibit significantly altered pharmacokinetics with respect to healthy subjects, while grade B impairment patients had significantly higher AUC and MRT. Tmax values pointed to reduced absorption rate in patients compared to healthy subjects; the changes were more evident in grade B than grade A patients, although statistical significance was not reached. The reduction in absorption rate in grade B patients is probably related to their higher mean age, since this effect has been reported for manidipine. The pharmacokinetics of manidipine seem only modified in patients with a certain degree of hepatic impairment (at least Pugh grade 6 and Child grade B); therefore, adaptation of the dosing regimen does not seem to be generally recommendable, but should be modulated according to the liver status of the patient.
Bio-Pharma S.A., Wavre, Belgium.
X
X
Deroubaix
R L
RL
Lins
S
S
Lens
A
A
Allemon
B
B
Jeanbaptiste
G
G
Poli
D
D
Acerbi
A
A
Stockis
P
P
Ventura
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D004095:Dihydropyridines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D008104:Liver Cirrhosis, Alcoholic / Q000145:classification / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009578:Nitrobenzenes; D010879:Piperazines; D012016:Reference Values; D012720:Severity of Illness Index
D000959:Antihypertensive Agents; D004095:Dihydropyridines; D009578:Nitrobenzenes; D010879:Piperazines; C054218:manidipine