Influence of cimetidine on pharmacokinetics of propranolol.

Heagerty, AM; Donovan, MA; Castleden, C. M.; Pohl, J.; Patel, L.; Hedges, A.

doi:10.1136/bmj.282.6280.1917

Cited by 84 publications

(16 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The bioavailability of cimetidine (Puurunen & Pelkonen, 1979), inlignocaine and of paracetamol is reduced in creases the bioavailability of propranolol (Feely patients taking anticonvulsant drugs known to et Heagerty et al, 1981) and chlorproduce enzyme induction (Perucca & Richens methiazole . Labetalol, a 1979a, b;Perucca et al, 1980).…”

Section: Introductionmentioning

confidence: 99%

The effects of enzyme induction and enzyme inhibition on labetalol pharmacokinetics.

Daneshmend¹,

Roberts²

1984

Brit J Clinical Pharma

View full text Add to dashboard Cite

The oral and intravenous pharmacokinetics of labetalol were determined in five subjects before and after a 3 week course of glutethimide 500 mg/day. After glutethimide there was a significant reduction in the AUC after the oral dose of labetalol, from 40,596 +/‐ 11,534 (mean +/‐ s.e. mean) to 22,057 +/‐ 6,276 ng ml‐1 min (2P less than 0.05), and systemic bioavailability was reduced from 30.3 +/‐ 2.8 to 17.0 +/‐ 3.5% (2P less than 0.001). There was no significant change in labetalol plasma concentration‐time curve (AUC) following an intravenous dose, half‐ life, volume of distribution, and plasma clearance. The oral and intravenous pharmacokinetics of labetalol were determined in six subjects before and after a 3 day course of cimetidine 1.6 g/day. After cimetidine there was a significant reduction in the volume of distribution of labetalol, from 520 +/‐ 51 to 445 +/‐ 24 1 (2P less than 0.05). The AUC of labetalol after the oral dose increased by 66%, from 51,029 +/‐ 7,950 to 84,772 +/‐ 19,444 ng ml‐1 min (2P = 0.06). The systemic bioavailability of labetalol increased from 25.1 +/‐ 2.4 to 39.0 +/‐ 7.6% (2P = 0.06). There was no significant change in labetalol AUC after the intravenous dose, half life, and plasma clearance. There were no significant changes in resting heart rate and supine systolic and diastolic blood pressure following labetalol plus glutethimide, or labetalol plus cimetidine.(ABSTRACT TRUNCATED AT 250 WORDS)

show abstract

Section: Introductionmentioning

confidence: 99%

The effects of enzyme induction and enzyme inhibition on labetalol pharmacokinetics.

Daneshmend¹,

Roberts²

1984

Brit J Clinical Pharma

View full text Add to dashboard Cite

show abstract

“…Castleden et al (1975) found that given the same oral dose, substantially greater plasma levels were attained in elderly subjects compared with younger ones. Heagerty et al (1981) showed that concurrent cimetidine therapy led to both a higher blood propranolol concentration and relative bioavailability. Patel et al (1983) demonstrated that the area under the curve for propranolol administered per vaginam was significantly greater than that after oral administration.…”

Section: Discussionmentioning

confidence: 99%

Propranolol pharmacokinetics during the menstrual cycle

Abdu-Aguye

Dunlop

Patel

et al. 1986

Postgraduate Medical Journal

View full text Add to dashboard Cite

Summary:The pharmacokinetics of propranolol during menstruation and in the mid menstrual cycle have been studied in nine young women taking a single 80 mg tablet on each occasion. There were wide between-individual differences in the serum concentration at any given time (4-5 fold at peak concentrations) but the serum concentration time curves within individuals showed only mild variations. The differences between the average pharmacokinetic parameter estimates for the group did not differ significantly between the two periods of study.

show abstract

“…Cimetidine is a potent inhibitor of the metabolism of a wide variety of drugs, including theophylline [10][11][12], acetaminophen [13][14][15], hexobarbital [16,17], aminopyrine [16][17][18], caffeine [18,19], phenacetin [18], phenytoin and antipyrine [20], warfarin [21], coumarin derivatives [22,23], benzo[a]pyrene [17,22], benzodiazepines [24], and propranolol [25]. The mechanism of inhibition of cimetidine, which has an imidazole ring struc ture, is unclear [reviewed in 1], The wide spectrum of drug metabolism that can be inhibited by cimetidine, however, is reminiscent of ellipticine, an antineoplastic agent which also elicits a strong type II difference spectrum and contains an imidazole ring [26].…”

Section: Discussionmentioning

confidence: 99%

Effects of Cimetidine on Theophylline, Acetaminophen, and Zoxazolamine Toxicity in the Intact Mouse

Lazarte¹,

Bigelow²,

Nebert³

et al. 1984

Dev Pharmacol Ther

View full text Add to dashboard Cite

3-Methylcholanthrene treatment of C57BL/6N mice induces significant amounts of cytochromes P(1)-450, whereas P(1)-450 levels in 3-methylcholanthrene-treated DBA/2N mice are no different from those in control C57BL/6N or DBA/2N mice. Comparison of 3-methylcholanthrene-treated C57BL/6N and DBA/2N mice -thus provides a convenient means of determining the role of P(1)-450 metabolism in two strains of mice following identical drug treatment regimens. 3-Methylcholanthrene-induced P(1)-450 is shown to be more effective than other forms of P-450 in detoxifying theophylline and zoxazolamine and in enhancing the toxicity of acetaminophen. Cimetidine in vivo blocks these metabolic pathways, resulting in increased toxicity of theophylline and zoxazolamine and protection against acetaminophen toxicity. These data illustrate the double-edged sword nature of P(1)-450 metabolism and the possibility of a paradoxical effect of cimetidine during drug-drug interactions in vivo. Cimetidine is shown to inhibit in vivo and in vitro the metabolism by both 3-methylcholanthrene-induced P(1)-450 and control forms of P-450; these data suggest that cimetidine may be acting at the level of P-450 reduction by NADPH-P-450 oxidoreductase. This same mechanism of action has been previously suggested for ellipticine.

show abstract

Influence of cimetidine on pharmacokinetics of propranolol.

Cited by 84 publications

References 14 publications

The effects of enzyme induction and enzyme inhibition on labetalol pharmacokinetics.

The effects of enzyme induction and enzyme inhibition on labetalol pharmacokinetics.

Propranolol pharmacokinetics during the menstrual cycle

Effects of Cimetidine on Theophylline, Acetaminophen, and Zoxazolamine Toxicity in the Intact Mouse

Contact Info

Product

Resources

About