The effects of age and renal impairment on the pharmacokinetics of co-administered lisinopril and hydrochlorothiazide.
The pharmacokinetics of combined lisinopril and hydrochlorothiazide have been studied following single and multiple oral doses to 'young' (reference), elderly and renally impaired hypertensive patients. Tablets containing the fixed combination of lisinopril 20 mg and hydrochlorothiazide 12.5 mg were administered as a single dose followed by daily administration for 6-8 days. Serum concentration and haemodynamic measurements were made at intervals up to 48 hours after the first and last doses. The serum profiles of both drugs were comparable with observations from previous studies, showing higher concentrations in the elderly and in the renally impaired patients. Similar differences have been reported for such patient groups when the drugs were administered separately, indicating an absence of pharmacokinetic interaction. Both drugs accumulated by about 30% on multiple daily dosing. There were no differences between the patient groups in the extent of accumulation. The combination of lisinopril and hydrochlorothiazide produced the expected hypotensive response, minimum BP values being recorded 4 and 6 hours after treatment. The higher concentrations in the elderly and renally impaired patients were not associated with a greater reduction in BP. The pharmacokinetic behaviour of lisinopril and hydrochlorothiazide given together to elderly and renally impaired hypertensive patients suggests that a fixed dose combination is appropriate and that no changes to the dosage regimen additional to those used for the individual agents are necessary.
Laher
M S
MS
James Connolly Memorial Hospital, Dublin, Eire, UK.
Mulkerrins
E
E
Hosie
J
J
Connell
P A
PA
Smith
R P
RP
Swaisland
A J
AJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000493:pharmacokinetics*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004338:Drug Combinations; D004656:Enalapril / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D007674:Kidney Diseases / Q000150:complications / Q000378:metabolism*; D017706:Lisinopril; D008297:Male; D008875:Middle Aged
D000806:Angiotensin-Converting Enzyme Inhibitors; D004338:Drug Combinations; D006852:Hydrochlorothiazide; D004656:Enalapril; D017706:Lisinopril