A pharmacokinetic interaction between roxithromycin and midazolam

Backman, Janne T.; Aranko, Kari; Himberg, Jaakko‐Juhani; Olkkola, Klaus T.

doi:10.1007/bf00196114

Cited by 33 publications

(13 citation statements)

References 21 publications

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“…They are also reported to cause many in vivo interactions with drugs that are substrates of CYP3A, and the severity of such interactions varies from macrolide to macrolide (Periti et al, 1992;Westphal, 2000). Whereas erythromycin and clarithromycin markedly affect the AUC of midazolam, a CYP3A substrate, in humans, the effect of azithromycin is reported to be small (Backman et al, 1994;Yeates et al, 1996;Zimmermann et al, 1996). Periti et al (1992) have classified troleandomycin and erythromycin, 14-carbon member ring macrolides, as belonging to the first group with a high drug interaction potential; clarithromycin and roxithromycin (14-carbon), midecamycin and josamycin (16-carbon) belong to the second group, with a low interaction potential; and azithromycin (15-carbon), rokitamycin, and spiramycin (16-carbon) represent the third group with no interaction potential.…”

Section: Discussionmentioning

confidence: 99%

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Prediction of the in Vivo Interaction Between Midazolam and Macrolides Based on in Vitro Studies Using Human Liver Microsomes

Ogihara²,

Kanamitsu³

et al. 2003

Drug Metab Dispos

139

106

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Section: Discussionmentioning

confidence: 99%

“…On the other hand, a relatively small increase, by a factor of 1.5 and 1.2, has been reported in the case of pretreatment with roxithromycin (300 mg o.d. for 6 days) (Backman et al, 1994) and azithromycin (500 mg o.d. for 3 days) , respectively.…”

mentioning

confidence: 99%

Prediction of the in Vivo Interaction Between Midazolam and Macrolides Based on in Vitro Studies Using Human Liver Microsomes

Ogihara²,

Kanamitsu³

et al. 2003

Drug Metab Dispos

139

106

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“…For example, rifampin pretreatment reduced the area under the drug's plasma concentration-time curve by 96% (224), whereas ketaconazole increased this parameter by 15-fold (200), and itraconazole also resulted in a large effect (139,200,226). More modest changes (two-to fourfold) were found following a single dose of grapefruit juice (181) and a period of erythromycin (161), clarithromycin (227), roxithromycin (228), fluconazole (144), or diltiazem (131) administration. By contrast, several days pretreatment with azithromycin (229)(230)(231) and terbinafine (226) had no effect on midazolam's metabolism.…”

Section: In Vivo Probes Of Cyp3a Activitymentioning

confidence: 95%

In Vitro and in Vivo Drug Interactions Involving Human Cyp3a

Thummel

Wilkinson

1998

Annu. Rev. Pharmacol. Toxicol.

762

515

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Cytochrome P4503A (CYP3A) is importantly involved in the metabolism of many chemically diverse drugs administered to humans. Moreover, its localization in high amounts both in the small intestinal epithelium and liver makes it a major contributor to presystemic elimination following oral drug administration. Drug interactions involving enzyme inhibition or induction are common following the coadministration of two or more CYP3A substrates. Studies using in vitro preparations are useful in identifying such potential interactions and possibly permitting extrapolation of in vitro findings to the likely in vivo situation. Even if accurate quantitative predictions cannot be made, several classes of drugs can be expected to result in a drug interaction based on clinical experience. In many instances, the extent of such drug interactions is sufficiently pronounced to contraindicate the therapeutic use of the involved drugs.

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“…The inhibitory activities of clarithromycin and erythromycin on midazolam metabolism were greater than that of roxithromycin in this study, suggesting that the in vitro metabolism results would reflect in vivo interactions. [8][9][10][11][12] Since the inhibitory activities of all tested macrolides on pranlukast metabolism were very weak, it is considered that the in vivo effects of macrolides on pranlukast metabolism would be small.…”

Section: Discussionmentioning

confidence: 99%

In Vitro Metabolism and Inhibitory Effects of Pranlukast in Human Liver Microsomes

Yoneda

Matsumoto

Sutoh

et al. 2009

Biological & Pharmaceutical Bulletin

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Cysteinyl leukotrienes (cysLTs) are 5-lipoxygenase pathway products of arachidonate that induce bronchoconstriction, vascular hyperpermeability, mucosal edema accumulation, and mucus secretion. [1][2][3] Pranlukast is a selective cysLTs receptor antagonist, and a 225 mg twice-daily dose has been used to treat bronchial asthma and allergic rhinitis in Japan.The absorption fraction of pranlukast in human is approximately 20%, based on the excretion ratio of the unchanged form in the feces following oral administration (the absolute bioavailability has not been reported). The terminal elimination half-life of pranlukast in plasma is approximately 2 h. Pranlukast is minimally excreted in the urine. The major metabolic pathway of pranlukast is shown in Fig. 1. The plasma-binding of pranlukast is more than 99%, and the major binding protein is albumin.To date, it has been very difficult to predict drug-drug interactions with pranlukast in the clinical setting due to a lack of information. Therefore, we conducted in vitro experiments using human liver microsomes to allow us to evaluate the potential for drug-drug interactions, based on the metabolism and the inhibitory effects of pranlukast. MATERIALS AND METHODS MaterialsPranlukast and 6-methyl-4-oxo-8-[4-(4-phenylbutoxy)benzoylamino]-2-(tetrazol-5-yl)-4H-1-benzopyran (ONO-RS-425, an internal standard for pranlukast), were synthesized at Ono Pharmaceutical Co., Ltd. (Osaka, Japan). a-Naphthoflavone, quinideine, 4-hydroxybenzoic acid n-butyl ester and 4-hydroxybenzoic acid n-amyl ester were purchased from Tokyo Chemical Industry Co., Ltd. (Tokyo, Japan). Tranylcypromine, terfenadine, metoprolol, tolbutamide, erythromycin and roxithromycin were pur- We investigated the metabolism of pranlukast, a selective leukotriene agonist, and the potential for drugdrug interactions. Although cytochrome P450 (CYP) 3A4 appeared to be the major cytochrome P450 isoform involved in the metabolism of pranlukast, the results suggested that pranlukast metabolism was inhibited less than 50% by ketoconazole, a reversible CYP3A4 inhibitor, or by anti-CYP3A4 antibodies. Irreversible macrolide CYP3A4 inhibitors, clarithromycin, erythromycin and roxithromycin, exhibited little effect on pranlukast metabolism. On the other hand, pranlukast reversibly inhibited CYP2C8 and/or 2C9, and CYP3A4, with K i values of 3.9 and 4.1 m mmol/l, respectively. The [I] in,max,u /K i ratios were 0.004 and 0.003, respectively. The K i values were about 300-fold greater than the [I] in,max,u , therefore it is suggested that, at clinical doses, pranlukast will not affect the pharmacokinetics of concomitantly administered drugs that are primarily metabolized by CYP2C8 and/or 2C9 or CYP3A4.

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A pharmacokinetic interaction between roxithromycin and midazolam

Cited by 33 publications

References 21 publications

Prediction of the in Vivo Interaction Between Midazolam and Macrolides Based on in Vitro Studies Using Human Liver Microsomes

Prediction of the in Vivo Interaction Between Midazolam and Macrolides Based on in Vitro Studies Using Human Liver Microsomes

In Vitro and in Vivo Drug Interactions Involving Human Cyp3a

In Vitro Metabolism and Inhibitory Effects of Pranlukast in Human Liver Microsomes

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