Urine flow-dependence of theophylline renal clearance in man
- 1 August 1982
- journal article
- research article
- Published by Springer Science and Business Media LLC in Journal of Pharmacokinetics and Biopharmaceutics
- Vol. 10 (4), 351-364
- https://doi.org/10.1007/bf01065168
Abstract
Theophylline renal clearance is highly dependent on urine flow rate and is neither concentration nor dose related. To examine the flow dependency, theophylline was adminstered in single doses (4.3 mg/kg to 8.6 mg/kg) to 14 volunteers. Seven of these volunteers participated in studies in which theophylline and metabolite concentrations were held constant at six different levels. Due to the diuretic effect of theophylline, its renal clearance contributed up to 70% of the time-averaged total clearance, dose/total area, in the first hour after a single dose. The contribution then dropped to 5% of the time-averaged total clearance when the normal urine flow rate was restored. As a consequence of extensive tubular reabsorption, the urine/plasma concentration ratio of theophylline varied with urine flow rate and approached the value of the unbound fraction in plasma. On assumption that the reabsorption is passive, a mathematical model was used to explain the urine flow dependence of reabsorption and, therefore, the renal clearance of theophylline.Keywords
This publication has 26 references indexed in Scilit:
- An Automated HPLC Assay for Simultaneous Quantitation of Methylated Xanthines and Uric Acids in UrineJournal of Chromatographic Science, 1982
- A method for estimating within-individual variability in clearance and in volume of distribution from standard bioavailability studiesJournal of Pharmacokinetics and Biopharmaceutics, 1982
- Pharmacokinetics of Theophylline in Hepatic DiseaseChest, 1978
- Clinical Pharmacokinetics of TheophyllineClinical Pharmacokinetics, 1978
- Dose-dependent kinetics of theophylline disposition in asthmatic childrenThe Journal of Pediatrics, 1977
- Renal Clearance of Theophylline in ManThe Journal of Clinical Pharmacology, 1976
- Mathematical simulation of normal nephron function in rat and manJournal of Theoretical Biology, 1971
- Pharmacokinetic Evidence for Saturable Renal Tubular Reabsorption of RiboflavinJournal of Pharmaceutical Sciences, 1970
- NONALDOSTERONE INFLUENCES ON RENAL SODIUM TRANSPORT*Annals of the New York Academy of Sciences, 1966
- Influence of Expansion of Extracellular Volume on Tubular Reabsorption of Sodium Independent of Changes in Glomerular Filtration Rate and Aldosterone Activity *JCI Insight, 1964