Drugs online research references
Clin Nephrol. 1995 Jan;43 Suppl 1:S24-6.
Saturable first-pass kinetics, plasma protein binding, and the furosemide intricacies.
Keller F.
Medical Department, University Hospital Ulm, Germany.
An equation for saturable nonlinear first-pass kinetics is presented to discuss some contra-intuitive findings encountered with furosemide bioavailability. The diverging effects on steady-state bioavailability (Fss) are simulated for changes in maximal metabolic capacity (Vm), volume of distribution (Vd), Michaelis constant (Km), steady-state plasma concentration (Css), repetitively administered drug dose (Dss), dosage interval (Tau), liver plasma flow (Ql), absorption rate constant (Ka), and free plasma fraction (fp), where (Cssf = fp Css = const.) and (Kmf = fp Km = const.). [Formula: see text] The present concept is in line with observations indicating that furosemide bioavailability decreases from 60 to 45% in nephrotic syndrome patients whose plasma protein binding is reduced and hepatic clearance increased. These observations and our equation-based simulations show that furosemide must have a first-pass effect. Hepatic extraction of furosemide is not facilitated by albumin, and saturable first-pass kinetics can not be used to explain an albumin paradox.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7781201&dopt=Abstract
Int J Clin Pharmacol Ther Toxicol. 1987 Mar;25(3):123-8.
Steady state absorption kinetics and pharmacodynamics of furosemide in congestive heart failure.
Chaturvedi PR, O'Donnell JP, Nicholas JM, Shoenthal DR, Waters DH, Gwilt PR.
Furosemide, a potent loop diuretic, is commonly used in the treatment of congestive heart failure (CHF). Unpredictability in the diuretic effect following oral doses has been attributed to variable and incomplete absorption and to variability in the pharmacodynamic response to furosemide. The present study is undertaken to investigate the absorption kinetics and pharmacodynamics of furosemide in patients with CHF during chronic medication. Ten patients with congestive heart failure were maintained on 40 to 160 mg furosemide for a month. The final dose at the end of this period was administered on an empty stomach. Plasma and urine were collected and assayed for furosemide, potassium, chloride, sodium and creatinine. Urine flow was also measured as a function of time. Plasma furosemide concentration-time data were fit to a two-compartment model with either two consecutive, discontinuous first order absorption rate constants or with a single monoexponential input; the former absorption model describing the data better than the latter. Average values of the half-life (205 +/- 28 min) and renal clearance (0.8 +/- 0.09 ml/min/kg) were similar to those reported by previous investigators. Drug excretion-response curves were lower and shifted to the right compared to data reported for normal subjects. Furthermore, a clockwise hysteresis was evident indicating acute within-dose tolerance.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3557737&dopt=Abstract
Clin Pharmacol Ther. 1982 Sep;32(3):303-6.
Hydralazine and furosemide kinetics.
Nomura A, Yasuda H, Katoh K, Akimoto T, Miyazaki K, Arita T.
Fursosemide kinetics were studied in 25 patients with congestive heart failure. The elimination half-life (t1/2) was longer and the elimination rate constant and the plasma clearance smaller in patients with advanced (n = 15) than in those with moderate (n = 10) failure. Furosemide kinetics with and without hydralazine were compared in eight patients with advanced heart failure. Furosemide t1/2 patients receiving both drugs fell from 96 +/- 16 to 81 +/- 15 min (P less than 0.02), elimination rate constant increased from 0.0186 +/- 0.0056 to 0.0214 +/- 0.0068 min -1 (P less than 0.05), and plasma clearance rose from 72.6 +/- 18.5 to 88.1 +/- 26.9 ml/min (P less than 0.01). Renal clearance rose from 45.4 +/- 12.0 to 60.9 +/- 19.0 ml/min (P less than 0.01) and creatinine clearance was unchanged. We conclude that hydralazine affects furosemide kinetics.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7105621&dopt=Abstract
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