Plasma propranolol concentrations and the erythrocyte sedimentation rate.

Schneider, R.; Bishop, H.; Hawkins, CF

doi:10.1111/j.1365-2125.1979.tb05907.x

Cited by 37 publications

(12 citation statements)

References 10 publications

(7 reference statements)

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“…Because plasma concentrations of some drugs are altered in patients with Crohn's disease, an in¯ammatory disease (Schneider et al 1979) and AA rats (Piquette-Miller and Jamali 1992, Shibata et al 1993, we investigated the e ect of arthritis on the pharmacokinetics of methotrexate using AA rats. M ethotrexate is mainly eliminated by excretion into the bile in rats (Masuda et al 1997) and therefore biliary excretion should regulate the disposition of methotrexate.…”

Section: Discussionmentioning

confidence: 99%

Decreased hepatobiliary transport of methotrexate in adjuvant arthritis rats

Achira¹,

Totsuka²,

Fujimura³

et al. 2002

Xenobiotica

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1. The pharmacokinetics, particularly the hepatobiliary transport of T-5557 ((3-methyl-2-oxo-piperadin-3-yl)-acetic acid N'-(3-thieophen-2-yl-8-methoxy-quinazolin-1-yl)-hydrazide), a novel anti-inflammatory agent, has been examined in normal and adjuvant arthritis (AA) rats. 2. Following oral administration of T-5557, the absolute bioavailability in AA rats was increased by sixfold compared with normal rats. The extent of binding T-5557 to plasma proteins obtained from AA rats was markedly greater than in normal rats (97.0 versus 88.2%). The biliary clearance in AA rats was significantly lower than that in normal rats (1.186 versus 5.621 ml min(-1) kg(-1)), and lower intrinsic biliary clearance was also observed in AA rats (40.33 versus 69.83 ml min(-1) kg(-1)). 3. Concomitant administration of T-5557 with quinidine, a potent P-glycoprotein inhibitor, to normal rats caused a significant decrease in the biliary clearance of T-5557 by 37.9%. Moreover, the transport of T-5557 for the apical-to-basal compartment in a Caco-2 cells' monolayer was fourfold lower than that for the opposite direction, and was increased in the presence of quinidine and verapamil. 4. These results suggest that P-glycoprotein is involved in the biliary excretion of T-5557 and the decrease in the transport activity as well as the increase in plasma protein binding caused the elevated plasma concentration and bioavailability of T-5557 in AA rats.

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Section: Discussionmentioning

confidence: 99%

Decreased hepatobiliary transport of methotrexate in adjuvant arthritis rats

Achira¹,

Totsuka²,

Fujimura³

et al. 2002

Xenobiotica

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“…Raised plasma propranolol concentrations (7-fold) were found when the drug was given orally to patients with rheumatoid arthritis or Crohn's disease (Schneider et al 1979). The increase in 313 concentrations was related to the increase in erythrocyte sedimentation rate.…”

Section: Inflammatory Diseasesmentioning

confidence: 97%

Individual Variation in First-Pass Metabolism

Tam

1993

Clinical Pharmacokinetics

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Individual variation in pharmacokinetics has long been recognised. This variability is extremely pronounced in drugs that undergo extensive first-pass metabolism. Drug concentrations obtained from individuals given the same dose could range several-fold, even in young healthy volunteers. In addition to the liver, which is the major organ for drug and xenobiotic metabolism, the gut and the lung can contribute significantly to variability in first-pass metabolism. Unfortunately, the contributions of the latter 2 organs are difficult to quantify because conventional in vivo methods for quantifying first-pass metabolism are not sufficiently specific. Drugs that are mainly eliminated by phase II metabolism (e.g. estrogens and progestogens, morphine, etc.) undergo significant first-pass gut metabolism. This is because the gut is rich in conjugating enzymes. The role of the lung in first-pass metabolism is not clear, although it is quite avid in binding basic drugs such as lidocaine (lignocaine), propranolol, etc. Factors such as age, gender, disease states, enzyme induction and inhibition, genetic polymorphism and food effects have been implicated in causing variability in pharmacokinetics of drugs that undergo extensive first-pass metabolism. Of various factors considered, age and gender make the least evident contributions, whereas genetic polymorphism, enzymatic changes due to induction or inhibition, and the effects of food are major contributors to the variability in first-pass metabolism. These factors can easily cause several-fold variations. Polymorphic disposition of imipramine and propafenone, an increase in verapamil first-pass metabolism by rifampicin (rifampin), and the effects of food on propranolol, metoprolol and propafenone, are typical examples. Unfortunately, the contributions of these factors towards variability are unpredictable and tend to be drug-dependent. A change in steady-state clearance of a drug can sometimes be exacerbated when first-pass metabolism and systemic clearance of a drug are simultaneously altered. Therefore, an understanding of the source of variability is the key to the optimisation of therapy.

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“…Higher than normal plasma propranolol concentrations have been reported in coeliac disease (Parsons et al, 1976;Schneider et al, 1976), Crohn's disease and rheumatoid arthritis (Schneider et al, 1979). Explanations which have been offered include increased absorption of the drug, improved bioavailability due to a reduction in 'first-pass' metabolism across the liver, or a change in the distribution volume of the drug.…”

Section: Intravenous Propranolol In Patients With Inflammationmentioning

confidence: 99%