Cimetidine pharmacokinetics

Nagai, N. Furahata, M. Ogata, H. Drug interactions between theophylline and H2-antagonists, roxa-tidine acetate hydrochloride and cimetidine Pharmacokinetic analysis in rats in vivo. Biol.Pharm.Bull., 1995,18, 1610-1613... 

Klotz U, Antilla V-J, Drug interactions with cimetidine pharmacokinetic studies to evaluate its m echanism, Namyn Schmiedebergs Arch Pharmacol (1980) 311, R77. 

A report briefly mentions a patient taking a beta blocker for angina who developed profound sinus bradycardia (36 bpm) and hypotension when cimetidine was also given. The beta blocker was not specified, but it was identified as atenolol elsewhere. Three well controlled studies in healthy subjects and patients found that cimetidine did not significantly alter blood levels of atenolol, nor did it alter the affect of atenolol on heart rate. Atenolol did not affect cimetidine pharmacokinetics. ... 

A study in 6 healthy subjects given metoprolol 100 mg twice daily for a week found that the cimetidine 1 g daily in divided doses increased the peak plasma levels of metoprolol by 70% and the AUC by 61%, but this did not increase the effect of metoprolol on the heart rate during exercise. " Metoprolol did not affect cimetidine pharmacokinetics. ... 

FIGURE 8.20 Drugs as subsets of clinical profiles. While burimamide, cimetidine, and metiamide are all active histamine H2 antagonists with ulcer healing activity burimamide lacks a suitable toxicity and pharmacokinetic profile and cimetidine is adequately absorbed but still toxic. Only metiamide fulfills the requirements of a clinically useful drug. 

Cheng-Prasoff relationship, 65-66, 214 Cholecystokinin receptor antagonists, 80 Cimetidine, 9-10 Clark, Alfred J., 3, 3f, 12, 41 Clark plot, 114 Clearance, 165—166 Clinical pharmacokinetics, 165 Cocaine, 149, 150f Competitive antagonism description of, 114 Gaddum equation for, 101-102, 113,... 

Rendic, S., Ruf, S., Weher, P. and Kajfez, F. (1984). Cimetidine and ranitidine Their interaction with human and pig liver microsomes and with purified cytochrome P-450. Eta J. Drug Metab. Pharmacokinet. 9 195-200. 

Toon S, Hopkins KJ, Garstang FM, et al. Comparative effects of ranitidine and cimetidine on the pharmacokinetics and pharmacodynamics of warfarin. Eur ] Clin Pharmacol 1987 32 165-72. 

Cimetidine, erythromycin, and dextropropoxyphene had no effect on the pharmacokinetics of MHD. Results with warfarin show no evidence of interaction with either single or repeated doses of oxcarbazepine. 

Eto, K., Y. Gomita, K. Furuno, K. Yao, M. Moriyama, and Y. Araki. Influences of cigarette smoke inhalation on pharmacokinetics of cimetidine in rats. DrugMetab Drug Interact 1991 9(2) 103-114. 

Clinicians should be aware of a few drug interactions with Zolpidem. Flumazenil acts as an antagonist to the hypnotic effects of zolpidem. There is decreased alertness when zolpidem is combined with cimetidine. There is an increase in anterograde amnesia in volunteers treated with a combination of imipramine and zolpidem. Haloperidol, ranitidine, chlorpromazine, warfarin, and digoxin, along with cimetidine and flumazenil, do not alter the pharmacokinetics of zolpidem (Salva and Costa, 1995). 

Practitioner errors sometimes occur because the physician does not appreciate the importance of changes in pharmacokinetics with age and age-related diseases. Some errors occur because the practitioner is unaware of incompatible drugs prescribed by other practitioners for the same patient. For example, cimetidine, an H2-blocking drug... 

Hatorp V, Thomsen MS. Drug interaction studies with repaglinide repaglinide on digoxin or theophylline pharmacokinetics and cimetidine on repaglinide pharmacokinetics. J Clin Pharmacol 2000 40(2) 184-92. 

There are numerous accounts in the literature of increased bioavailability in animals when changing the solid state. Kato and Kohetsu (1981) showed that form II amobarbital is more rapidly absorbedn vivo than form I. Dissolution rate experiments in water at(3"Showed a 1.6 times faster dissolution ratei vitro for form II compared to form I. Yokoyama et al. (1981) found that form III of 6-mercaptopurine was 1.5 times as bioavailable in rabbits as form I. It was six to seven times as soluble as the form I polymorph in studies by Kuroda et al. (1982). Kokubu et al. (1987) examined the therapeutic effect of different polymorphs of cimetidine in inhibition of ulcers in the rat. Pharmacokinetic studies found that form C was 1.4-1.5 times as bioavailable as forms A and B. This translated into a greater protection against stress ulceration, as shown in Table 19.4. The effec of form C was signiLcant compared to forms A, B, and D, which were all equivalent. 

Donepezil is both excreted in the urine intact and extensively metabolized to four major metabolites, two of which are known to be active, and a number of minor metabolites, not all of which have been identified. Three of the human metabolites of donepezil have not undergone extensive safety tests in animals. These comprise two O-demethylated derivatives and an N-oxidation product. Donepezil is metabolized by CYP 450 isoenzymes 2D6 and 3A4 and undergoes glucuronidation. The rate of metabolism of donepezil is slow and does not appear to be saturable. These findings are consistent with the results from formal pharmacokinetic studies which showed that donepezil and/or its metabolites do not inhibit the metabolism of theophylline, warfarin, cimetidine, or digoxin... 

P.J. Tiseo, C.A. Perdomo, L.T. Friedhoff, Concurrent administration of donepezil HC1 and cimetidine assessment of pharmacokinetic changes following single and multiple doses, Br. J. Cline. Pharmacol. 46 (1998) 25-29. 

Ebert U, Thong NQ, Oertel R, et al. Effects of rifampicin and cimetidine on pharmacokinetics and pharmacodynamics of lamotrigine in healthy subjects. Eur J Clin Pharmacol 2000 56(4) 299-304. 

Yasui-Furukori N, Uno T, Sugawara K, et al. Different effects of three transporting inhibitors, verapamil, cimetidine, and probenecid, on fexofenadine pharmacokinetics. Clin Pharmacol Ther 2005 77 17-23. 

S.R. Smith, and M.J. Kendall, Ranitidine versus cimetidine A comparison of their potential to cause clinically important drug interactions. Clin. Pharmacokinet. 15 44-56, 1988. 

Figure 2.20. Pharmacokinetic parameters and stractures of cimetidine and phenobarbital...

Pharmacokinetics" the label indicates that "following I.V. or I.M. administration, approximately 75% of the drug is recovered from the urine after 24 hours as the parent compound" (14). Since only one-fourth of the dose is eliminated by nonrenal mechanisms, it can be expected that functionally anephric patients who receive half the usual cimetidine dose, such as the man in the case presented at the beginning of this chapter, will have potentially toxic blood levels that are twice those recommended for patients with normal renal function. 

Grahnen A, von Bahr C, Lindstrom B, Rosen A. Bioavailability and pharmacokinetics of cimetidine. Eur J Clin Pharmacol 1979 16 335-40. 

Veng Pedersen P, Miller R. Pharmacokinetics and bioavailability of cimetidine in humans. J Pharm Sci 1980 69 394-8. 

Pharmacokinetics. Carbamazepine is extensively metabolised one of the main products, an epoxide (a chemically reactive form), has anticonvulsant activity similar to that of the parent drug but may also cause some of its adverse effects. The t) of carbamazepine falls from 35 h to 20 h over the first few weeks of therapy due to induction of hepatic enzymes that metabolise it as well as other drugs, including corticosteroids (adrenal and contraceptive), theophylline and warfarin. Cimetidine and valproate inhibit its metabolism. There are complex interactions with other antiepilepsy drugs, which constitute a reason for monodrug therapy. 

Pharmacokinetic. Agents metabolised in the liver provide higher plasma concentrations when another drug that inhibits hepatic metabolism, e.g. cimetidine, is added. Enzyme inducers enhance the metabolism of this class of P-blockers. P-adrenoceptor blockers themselves reduce hepatic blood flow (fall in cardiac output) and reduce the metabolism of p-blockers and other drugs whose metabolic elimination is dependent on the rate of delivery to the liver, e.g. lignocaine (lidocaine), chlorpromazine. 

Measurement of underivatized propranolol enantiomers in serum using a celluIose-tris(3,5-dimethylphenylcarbamate) high performance liquid chromatographic (HPLC) chiral stationary phase" (54). A method for the direct measurement of the enantiomers of propranolol in human serum was developed using the OD CSP and a mobile phase composed of hexane 2-propranol W,W-dimethyloctylamine (92 8 0.01, v/v/ v). The assay was validated for use in pharmacokinetic and metabolic studies and was subsequently used in the investigation of the effect of cimetidine on the metallism and clearance of propranolol enantiomers (60). 

A retrospective analysis of 3995 patients treated with azithromycin did not show any pharmacokinetic interactions in patients who were also taking various other drugs, including cimetidine (1,45). 

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