Influence of First-Pass Effect on Availability of Drugs on Oral Administration

Gibaldi, Milo; Boyes, R. N.; Feldman, Stuart

doi:10.1002/jps.2600600909

Cited by 262 publications

(95 citation statements)

References 4 publications

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“…alprenolol (von Bahr, Alvan, Lind, Mellstr6m & Sjoqvist, 1974;Regardh, 1975), metoprolol (Regardh, 1975;Johnsson, Regardh & S6lvell, 1975) propranolol (Shand & Rangno, 1972;Coltart, 1975;Paterson, Conolly, Dollery, Hayes & Cooper, 1970). For oxprenolol (Riess, Brechbuehler, Brunner, Imhof & Jack, 1975) the first-pass effect, which is independent of the dose, yields a value of 50-60% when calculated according to the method proposed by Gibaldi, Boyes & Feldman (1971). This formula can be applied when intravenous data are not available and when the drug is eliminated mainly by metabolism as in the case of oxprenolol (Riess et al, 1975).…”

Section: Pindolol Ap-adrenoceptor Blocking Agent With a Negligible Fmentioning

confidence: 99%

Pindolol, a beta‐adrenoceptor blocking agent with a negligible first‐ pass effect.

Meier¹,

Nüesch²

1977

Brit J Clinical Pharma

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Section: Pindolol Ap-adrenoceptor Blocking Agent With a Negligible Fmentioning

confidence: 99%

Pindolol, a beta‐adrenoceptor blocking agent with a negligible first‐ pass effect.

Meier¹,

Nüesch²

1977

Brit J Clinical Pharma

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“…Whereas enzyme induction has a negligible effect on the serum half-life of these compounds, it markedly reduces their systemic availability after oral administration (Gibaldi, Boyes & Feldman, 1971;Rowland, 1972; Perrier & Gibaldi, 1974;Wilkinson & Shand, 1975). Although the theoretical aspects of this phenomenon have been carefully analysed, very little experimental evidence is available in man (Meikle, Jubiz, Matsukura, West & Tyler, 1969;Alvan, Piafsky, Lind & von Bahr, 1977).…”

Section: Introductionmentioning

confidence: 99%

Paracetamol disposition in normal subjects and in patients treated with antiepileptic drugs.

Perucca¹,

Richens²

1979

Brit J Clinical Pharma

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1 The serum concentration profile of paracetamol has been determined after administration of single 1000 mg intravenous and oral doses in six normal subjects and six epileptic patients on chronic antiepileptic drug therapy. The urinary excretion of free and conjugated paracetamol has also been determined. 2 Following intravenous administration, serum paracetamol concentration declined with first‐order kinetics. Both elimination rate and total body clearance were higher in the epileptic patients, although in neither case was the difference statistically significant. 3 The oral bioavailability (mean +/‐ s.e. mean) was significantly lower in the epileptic patients than in the normal subjects (0.77 +/‐ 0.03 and 0.89 +/‐ 0.02 respectively, P less than 0.01), whereas the urinary excretion total (free+conjugated) paracetamol was almost identical in the two groups. 4 It is suggested that the lower bioavailability of paracetamol in the epileptic patients results from enhancement of first‐pass metabolism, secondary to enzyme induction.

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“…The perfusion limited pharmacokinetic model (Gibaldi, Boyes & Feldman, 1971;Rowland, 1972;Rowland, Benet & Graham, 1973;Wilkinson, 1975;Wilkinson & Shand, 1975) has recently been successfully applied to describe the disposition kinetics of high clearance drugs such as nortriptyline (Alvin, BorgA, Lind, Palmer & Siwers, 1977), alprenolol (Alvan, Piafsky, Lund & von Bahr, 1977) and paracetamol (Perucca & Richens, 1978) in man. According to this model, the systemic clearance of drugs subject to high hepatic extraction is mainly determined by the rate of liver blood flow (LBF) and only marginally influenced by changes in the activity of the hepatic drug metabolizing enzymes.…”

Section: Introductionmentioning

confidence: 99%

Reduction of oral bioavailability of lignocaine by induction of first pass metabolism in epileptic patients.

Perucca¹,

Richens²

1979

Brit J Clinical Pharma

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1 The pharmacokinetics of lignocaine following single oral and intravenous doses have )een investigated in six normal volunteers and in six patients receiving chronic antiepile tic drug therapy. 2 After intravenous administration, serum lignocaine levels declined biexponentially in all subjects. The serum clearance (mean + s.d.) was slightly higher in the patients (0.85 + 0.09 v 0.77 + 0.07 1/min) but the difference was not statistically significant. 3 Lignocaine bioavailability after oral administration was more than two-fold lower in the patients than in the normal subjects (0.15 +0.06 v 0.37 +0.09, P < 0.001). 4 It is suggested that the reduced bioavailability of lignocaine in the patients is a consequence of stimulation of hepatic first-pass metabolism by antiepileptic drugs.

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Influence of First-Pass Effect on Availability of Drugs on Oral Administration

Cited by 262 publications

References 4 publications

Pindolol, a beta‐adrenoceptor blocking agent with a negligible first‐ pass effect.

Pindolol, a beta‐adrenoceptor blocking agent with a negligible first‐ pass effect.

Paracetamol disposition in normal subjects and in patients treated with antiepileptic drugs.

Reduction of oral bioavailability of lignocaine by induction of first pass metabolism in epileptic patients.

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