Population pharmacokinetic modeling of furosemide in patients with hypertension and fluid overload conditions.
BACKGROUND
Furosemide is a loop diuretic drug frequently indicated in hypertension and fluid overload conditions such as congestive heart failure and hepatic cirrhosis.


OBJECTIVE
The purpose of the study was to establish a population pharmacokinetic model for furosemide in Indian hypertensive and fluid overload patients, and to evaluate effects of covariates on the volume of distribution (V/F) and oral clearance (CL/F) of furosemide.


METHODS
A total of 188 furosemide plasma sample concentrations from 63 patients with hypertension or fluid overload conditions were collected in this study. The population pharmacokinetic model for furosemide was built using Phoenix NLME 1.3 software. The covariates included age, sex, body surface area, bodyweight, height and creatinine clearance (CRCL).


RESULTS
The pharmacokinetic data of furosemide was adequately explained by a two-compartment linear pharmacokinetic model with first-order absorption and an absorption lag-time. The mean values of CL/F and Vd/F of furosemide in the patients were 15.054Lh-1and 4.419L, respectively. Analysis of covariates showed that CRCL was significantly influencing the clearance of furosemide.


CONCLUSIONS
The final population pharmacokinetic model was demonstrated to be appropriate and effective and it can be used to assess the pharmacokinetic parameters of furosemide in Indian patients with hypertension and fluid overload conditions.
Drug Metabolism and Clinical Pharmacokinetics Division, Department of Pharmacology, University College of Pharmaceutical Sciences, Kakatiya University, Warangal, Telangana, India.
Devender
D
Kodati
Drug Metabolism and Clinical Pharmacokinetics Division, Department of Pharmacology, University College of Pharmaceutical Sciences, Kakatiya University, Warangal, Telangana, India. Electronic address: ynrucpsc@gmail.com.
Narsimhareddy
N
Yellu
D000328:Adult; D000368:Aged; D001826:Body Fluids / Q000378:metabolism; D004232:Diuretics / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D005665:Furosemide / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D007194:India; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D014018:Tissue Distribution
D004232:Diuretics; D005665:Furosemide
Furosemide; Hypertension; Phoenix NLME; Population pharmacokinetics