Effect of Parallel First-Order Drug Loss from Site of Administration on Calculated Values for Absorption Rate Constants

Notari, Robert E.; Deyoung, Joyce L.; Reuning, Richard H.

doi:10.1002/jps.2600610133

Cited by 37 publications

(3 citation statements)

References 3 publications

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“…The derivatives are separated from excess reagent by solvent extraction and finally determined by electron-capture GLC. This method is tedious, and the use of theobromine as an internal standard is not a good choice because it is present in beverages such as tea and cocoa and is a metabolite of caffeine (16)(17)(18).…”

Section: Resultsmentioning

confidence: 99%

Pharmacokinetics of Topically Applied Pilocarpine in the Albino Rabbit Eye

Makoid

Robinson

1979

Journal of Pharmaceutical Sciences

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Section: Resultsmentioning

confidence: 99%

Pharmacokinetics of Topically Applied Pilocarpine in the Albino Rabbit Eye

Makoid

Robinson

1979

Journal of Pharmaceutical Sciences

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“…The apparent rate of absorption was examined from the slope of the rate of bioavailability derived from the Loo & Riegelman (1968) calculation taking into account the lag time and the fraction of dose systemically bioavailable (Notari, DeYoung & Reuning, 1972).…”

Section: Pharmacokinetic Analysismentioning

confidence: 99%

Absorption and bioavailability of oral erythromycin.

Mather

Austin

Philpot

et al. 1981

Brit J Clinical Pharma

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1 Extent and rate of absorption of erythromycin were studied in 24 healthy volunteers whose disposition kinetics after i.v. injections had been previously documented. 2 Two clinically attractive oral dosage regimens were administered: erythromycin stearate tablets 1 h before meals (Regimen A), and erythromycin base capsules 30 min after start of meals (Regimen B), each equivalent to erythromycin 250 mg, 6 h apart for 9 doses. 3 Serum concentrations of erythromycin measured during the 1st and 9th (steady-state) dosing intervals resulted in higher maximum serum concentrations for Regimen A (median 1.1, range 0-3.3 and 2.7, 0.6-7.3 mg/l for Doses 1 and 9, respectively) compared with Regimen B (0.4, 0-2.2 and 1.4, 0.2-4.9 mg/l). 4 Absorption occurred earlier with Regimen A with times to maximum concentrations (median, range) being 128, 60-greater than 360 and 118, 75-210 min for doses 1 and 9 respectively, (lag times 75, 15- greater than 360 and 73, 10-110 min) compared with 303, 130-greater than 360 and 173, 45-greater than 360 min (lag times 183, 70-greater than 360 and 190, 20-330 min) for Regimen B. 5 Where it could be assessed, absolute bioavailability for Regimen A was approximately 30% (Dose 1) and 65% (Dose 9) and 40% for both doses of Regimen B. 6 Whereas individual serum concentration-time curves were accurately predicted by the mean for Regimen A, predictability for Regimen B was impossible due to prolonged and variable lag time. 7 The large intersubject variability in erythromycin serum concentration after oral administration, has been shown conclusively to be related to variability in absorption kinetics and absolute bioavailability rather than to variability in disposition kinetics.

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“…If the plot is curved, or contains curved or linear segments, it may often be resolved to yield the components of the rate d %At~dr." Notari et al (3), Perrier and Gibaldi (4), and Leeson and Weintraub (5) have discussed problems that arise in estimating "absorption rate constants" when the drug is absorbed and also simultaneously lost to an extravascular compartment via either a parallel first-order or a zero-order process. Loo and Riegelman (6) applied the Wagner-Nelson method (1) to data which obviously obeyed the two-compartment open model with both first-order and zero-order input to the central compartment and stated : "It appears that both the bi-exponential and the occasional appearance of maxima are artifacts of the numerical method."…”

Section: Introductionmentioning

confidence: 99%

Application of the Wagner-Nelson absorption method to the two-compartment open model

Wagner

1974

Journal of Pharmacokinetics and Biopharmaceutics

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This report considers the application of the W'agner-Nelson method to both one-and two-compartment open model data when there is no competing reaction at the absorption site. Equations are derived which show that application of the Wagner-Nelson method to data which obey the twocompartment open model with first-order absorption allows accurate estimation of not only the rate constant k, but also the parameters of the two-compartment open model, namely k~2, k21 , and ket. In the example given, this new method was more accurate than the classical "feathering" or "back-projection" method. The appropriate criterion for "collapsing" the two-to the onecompartment open model is given. In cases where the one-compartment open model applies, and absorption is first order but abruptly ceases after some time, it is shown that k a may be accurately estimated by application of the Guggenheim method to the Ar/V values calculated for the absorption phase.

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Effect of Parallel First-Order Drug Loss from Site of Administration on Calculated Values for Absorption Rate Constants

Cited by 37 publications

References 3 publications

Pharmacokinetics of Topically Applied Pilocarpine in the Albino Rabbit Eye

Pharmacokinetics of Topically Applied Pilocarpine in the Albino Rabbit Eye

Absorption and bioavailability of oral erythromycin.

Application of the Wagner-Nelson absorption method to the two-compartment open model

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