What question did this study set out to answer?

To characterize the elimination kinetics and metabolic pathways of theophylline and its major metabolites across therapeutic concentration levels.

March 1, 1982Clinical Pharmacology & Therapeutics

Nonlinear theophylline elimination

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Authors

DTD. Dan-Shya Tang-LiuAllergan (United States)RWRoger WilliamsRutgers, The State University of New Jersey SRSidney RiegelmanUniversity of Southern California

Discussion

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Implication

Pharmacokinetic study reveals capacity-limited theophylline elimination in healthy adults, indicating saturable metabolism within standard therapeutic concentrations.

Key Points

To characterize the elimination kinetics and metabolic pathways of theophylline and its major metabolites across therapeutic concentration levels.
Assessed theophylline pharmacokinetics in 14 healthy adults using single-dose and multiple-plateau experimental protocols.
Quantified plasma and urine levels of theophylline, 3-methylxanthine (3-MX), 1-methyluric acid (1-MU), and 1,3-dimethyluric acid (13-MU) down to approximately 0.020 mg/l.
Modeled metabolite formation rates using non-linear Michaelis-Menten computer curve fitting.
Metabolite formation followed Michaelis-Menten kinetics with mean Vmax values of 5 mg/hr (3-MX), 13 mg/hr (1-MU), and 34 mg/hr (13-MU), and half-saturation constants of 2.7 mg/l, 9.3 mg/l, and 14.2 mg/l, demonstrating capacity limitation within the therapeutic window.
Renal clearance was 12.0 ± 1.3 l/hr for 3-MX, 22.5 ± 1.5 l/hr for 1-MU, and 22.6 ± 1.6 l/hr for 13-MU, while parent drug renal excretion depended strongly on urine flow rate.
Diuresis and early drug distribution counterbalanced the saturable metabolic clearance, producing an initial pseudo-log-linear plasma decay before displaying convex-descending kinetics below 1 mg/l.

Cite This Study

Tang–Liu et al. (1982) studied this question.

synapsesocial.com/papers/6ab0eab25f937fa5beca57f4 https://doi.org/10.1038/clpt.1982.46

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March 1, 1982Clinical Pharmacology & Therapeutics

Nonlinear theophylline elimination

View Full Paper

Ask AI

Bookmark

Authors

DTD. Dan-Shya Tang-LiuAllergan (United States)RWRoger WilliamsRutgers, The State University of New Jersey SRSidney RiegelmanUniversity of Southern California

Discussion

Member takes

Implication

Pharmacokinetic study reveals capacity-limited theophylline elimination in healthy adults, indicating saturable metabolism within standard therapeutic concentrations.

Key Points

To characterize the elimination kinetics and metabolic pathways of theophylline and its major metabolites across therapeutic concentration levels.
Assessed theophylline pharmacokinetics in 14 healthy adults using single-dose and multiple-plateau experimental protocols.
Quantified plasma and urine levels of theophylline, 3-methylxanthine (3-MX), 1-methyluric acid (1-MU), and 1,3-dimethyluric acid (13-MU) down to approximately 0.020 mg/l.
Modeled metabolite formation rates using non-linear Michaelis-Menten computer curve fitting.
Metabolite formation followed Michaelis-Menten kinetics with mean Vmax values of 5 mg/hr (3-MX), 13 mg/hr (1-MU), and 34 mg/hr (13-MU), and half-saturation constants of 2.7 mg/l, 9.3 mg/l, and 14.2 mg/l, demonstrating capacity limitation within the therapeutic window.
Renal clearance was 12.0 ± 1.3 l/hr for 3-MX, 22.5 ± 1.5 l/hr for 1-MU, and 22.6 ± 1.6 l/hr for 13-MU, while parent drug renal excretion depended strongly on urine flow rate.
Diuresis and early drug distribution counterbalanced the saturable metabolic clearance, producing an initial pseudo-log-linear plasma decay before displaying convex-descending kinetics below 1 mg/l.

Cite This Study

Tang–Liu et al. (1982) studied this question.

synapsesocial.com/papers/6ab0eab25f937fa5beca57f4 https://doi.org/10.1038/clpt.1982.46

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