Pharmacokinetics of Drug Disposition: Hemodynamic Considerations

Wilkinson, Grant R.

doi:10.1146/annurev.pa.15.040175.000303

Cited by 119 publications

(43 citation statements)

References 50 publications

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“…After physical stress, changes in cardiac output can be observed. This can influence a drug's disposition via changes in an organ's or tissue's blood perfusion (Wilkinson, 1975). Hepatic elimination can be modified by changes in hepatic blood flow (Rowland, Benet & Graham, 1973) and during exercise this flow decreases.…”

Section: Physical Exercise and Disposition Of Diazepammentioning

confidence: 99%

Physical Exercise and Disposition of Diazepam

Klotz

Lucke

1978

Brit J Clinical Pharma

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Section: Physical Exercise and Disposition Of Diazepammentioning

confidence: 99%

Physical Exercise and Disposition of Diazepam

Klotz

Lucke

1978

Brit J Clinical Pharma

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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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“…As well, subjects rested in a seated position on each study day until after the 11 h blood sample was drawn. These food and posture/exercise restrictions were done to eliminate, as much as possible, these factors as potential study interferences secondary to their effect on hepatic blood flow (Wilkinson, 1975).…”

Section: Patientsmentioning

confidence: 99%

Ranitidine does not alter pethidine disposition in man.

Guay¹,

Meatherall²,

Chalmers³

et al. 1985

Brit J Clinical Pharma

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The effect of concurrent ranitidine administration on the disposition of pethidine was investigated in eight healthy male volunteers (19‐33 years). The subjects received 70 mg i.v. pethidine HCl doses before and during ranitidine treatment (150 mg p.o. twice daily). Ranitidine therapy was not associated with significant alterations in pethidine elimination rate constant, volume of distribution at steady state, total body clearance, and 24 h urinary excretion. No alteration in pethidine oxidation to norpethidine was noted, as suggested by nonsignificant changes in lag time to appearance of quantifiable norpethidine in serum, time to peak concentration, peak concentration, area under the curve from time 0.24 h, and 24 h urinary excretion. It would appear that, unlike cimetidine, ranitidine does not interact pharmacokinetically with pethidine. Further studies are necessary to evaluate the potential clinical advantages of ranitidine vs cimetidine therapy in patients also receiving pethidine.

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Pharmacokinetics of Drug Disposition: Hemodynamic Considerations

Cited by 119 publications

References 50 publications

Physical Exercise and Disposition of Diazepam

Physical Exercise and Disposition of Diazepam

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

Ranitidine does not alter pethidine disposition in man.

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