Influence of liver disease on the elimination of drugs

Klotz, Ulrich

doi:10.1007/bf03189267

Cited by 19 publications

(2 citation statements)

References 69 publications

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“…These results agree with those of previous studies which have shown that oxidative drug metabolism in general may be affected by hepatic cirrhosis (Klotz 1976). However, these patients with cirrhosis were older (40 to 80 years) than the healthy volunteers (19 to 31 years) which were used for comparisons.…”

supporting

confidence: 93%

Pharmacokinetics of [14C]Omeprazole in Patients with Liver Cirrhosis

Andersson

Olsson

Regårdh

et al. 1993

Clinical Pharmacokinetics

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The pharmacokinetics of omeprazole and its metabolites following single doses were studied in 8 patients with liver cirrhosis. Each patient participated in 2 experiments in which [14C]omeprazole was administered either intravenously (20mg) or in an oral solution (40mg) in a randomised crossover design. Plasma concentrations of omeprazole and 2 of its identified metabolites, as well as total radioactivity were followed for 24h; urinary excretion was followed for 96h. The mean elimination half-life of omeprazole in the patients with cirrhosis was 2.8h and the mean total plasma clearance was 67 ml/min (4.02 L/h); corresponding values from separate studies in young healthy volunteers were 0.7h and 594 ml/min (35.64 L/h). The mean systemic availability was nearly 100% in the patients with cirrhosis whereas the previously reported value in young volunteers was only 56%. Almost 80% of a given dose was excreted as urinary metabolites in both patients and young volunteers. It is concluded that, as the hepatic clearance of omeprazole was substantially reduced in these patients, the dose of omeprazole needed for a certain degree of acid suppression is lower in patients with liver cirrhosis.

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supporting

confidence: 93%

Pharmacokinetics of [14C]Omeprazole in Patients with Liver Cirrhosis

Andersson

Olsson

Regårdh

et al. 1993

Clinical Pharmacokinetics

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“…Alcohol abusers are often affected by changes * To whom correspondence should be addressed in their liver function tests and it is well known that the pharmacokinetics of drugs eliminated primarily by hepatic metabolism can change significantly in patients with liver disease (Klotz 1976). For instance, alterations in liver blood flow, intrinsic clearance and serum protein binding may result in increased steady-state plasma lcvels of such drugs administered in the usual therapeutic doses.…”

mentioning

confidence: 99%

Pharmacokinetics of Zimeldine in Male Alcoholics

Gottfries

Grind²,

Lundström³

et al. 1986

Acta Pharmacologica et Toxicologica

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The pharmacokinetics of zimeldine, a 5‐HT reuptake blocker with antidepressive effects, was studied after a single oral dose and after multiple oral administration in 19 alcoholic males, 10 with and 9 without chronic liver damage. The average plasma concentration of zimeldine as assessed by the AUC values (area under the plasma concentration‐time curve) was significantly higher in the chronically liver damaged patients than in the patients without chronic liver damage. The plasma half‐life of zimeldine was also significantly longer in the chronically liver damaged patients. There were no differences in the obtained pharmacokinetic parameters between the patients having nonchronic liver damage and healthy control subjects. The pharmacokinetics of the active metabolite norzimeldine (resulting from N‐demethylation of zimeldine) showed no differences between the two groups of alcoholics and the healthy controls. The IgA values were significantly correlated to both the AUC and plasma half‐life of zimeldine. No other correlation between clinical chemistry parameters and pharmacokinetic parameters of zimeldine and norzimeldine were found.

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Effects of liver disease on urinary excretion of methadone and metabolites in maintenance patients: Quantitation by direct probe chemical ionization mass spectrometry

Kreek

Bencsath

Field

1980

Biol. Mass Spectrom.

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This study was performed to define the amounts of methadone and metabolites excreted in urine in otherwise healthy maintenance patients, and to determine whether the metabolism and elimination of methadone, as assessed by analyses of urines, is altered in patients with liver disease. A method was developed for the simultaneous quantitation of methadone and six of its major and minor metabolites using chemical ionization mass spectrometry with direct probe introduction to increase sensitivity for analyses of the minor metabolites. Analyses of urine from unmedicated volunteers showed that the interferences at the mass range of interest (264-326) were usually small and therefore would not introduce significant error into analysis. Nineteen patients well-stabilized in chronic long-term methadone treatment were studied, five otherwise healthy males and fourteen patients with chronic liver disease (nine males and four females). Twenty-four hour urine collections were made and analyzed following extraction procedures. The concentrations of methadone and the major pyrrolidine metabolite exceeded 1 microgram ml-1 in all cases; the concentration (listed in descending order) of pyrrolidone, pyrroline, hydroxymethadone, hydroxypyrroline, methadol and hydroxypyrrolidine were all less than 1 microgram ml-1. The total 24 hour urinary excretion of methadone and its metabolites was 48.3% (+/- 1.71 SEM) in otherwise healthy patients but was significantly lower, 32.6% (+/- 3.19 SEM) in patients with liver disease (p less than 0.05). The total 24 hour excretion of the pyrrolidone metabolite, the end product of two pathways of methadone metabolism, was also significantly reduced in patients with liver disease (p less than 0.05). Females with liver disease had significantly higher ratios of pyrrolidine to methadone than did males with liver disease (p less than 0.05).

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Influence of liver disease on the elimination of drugs

Cited by 19 publications

References 69 publications

Pharmacokinetics of [14C]Omeprazole in Patients with Liver Cirrhosis

Pharmacokinetics of [14C]Omeprazole in Patients with Liver Cirrhosis

Pharmacokinetics of Zimeldine in Male Alcoholics

Effects of liver disease on urinary excretion of methadone and metabolites in maintenance patients: Quantitation by direct probe chemical ionization mass spectrometry

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