Concomitant Administration of Cyclosporin and Ketoconazole in Renal Transplant Recipients

First, M. Roy; Weiskittel, P; Alexander, J. Wesley; Schroeder, T. J.; Myre, Steven A.; Pesce, A J

doi:10.1016/s0140-6736(89)91802-3

Cited by 73 publications

(30 citation statements)

References 8 publications

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“…should occur within 24 h of exposure to the inducer, and should be largely gone within 3 d of removal of the inducer. It should be pointed out that it is not possible to exclude the presence or induction of P450IIIA3 in enterocytes based on our data.…”

Section: Discussionmentioning

confidence: 99%

“…CsA has been shown to be metabolized by P4501IIA4 in the liver (3,4,14). Drugs that inhibit P450IIIA4 activity in liver, such as erythromycin or ketoconazole (20), can significantly elevate CsA blood levels in patients (23,24). Conversely, many drugs that induce P450111A4 in liver, such as rifampin, can decrease CsA blood levels in patients (25).…”

Section: Introductionmentioning

confidence: 99%

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Identification of rifampin-inducible P450IIIA4 (CYP3A4) in human small bowel enterocytes.

et al. 1992

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Enzymes within the P450IIIA (CYP3A) subfamily appear to account for significant "first pass" metabolism of some drugs in the intestine. To identify which of the known P450IIIA genes are expressed in intestine, enterocyte RNA was hybridized on Northern blots with synthetic oligonucleotides complementary to hypervariable regions of hepatic P450IIIA4, P450IIIA5, and P450111A7 cDNAs. Hybridization was detected only with the P450IIIA4-specific oligonucleotide. The identity of the hybridizing mRNA was confirmed to be P45011IA4 by direct sequencing of a DNA fragment amplified from enterocyte cDNA by the polymerase chain reaction. To determine if enterocyte P450IIIA4 is inducible, biopsies of small bowel mucosa were obtained from five volunteers before and after they received 7 d of treatment with rifampin, a known inducer of P4501IIA4 in liver. Rifampin treatment resulted in a five-or eightfold mean increase (P < 0.05) in the biopsy concentration of P450IIIA4 mRNA when normalized for content of sucrase isomaltase or intestinal fatty acid binding protein mRNAs, respectively. Rifampin also induced P450II1A immunoreactive protein in enterocytes in each of the subjects, as judged by immunohistochemistry, and resulted in a 10-fold increase in P450IIIA4-specific catalytic activity (erythromycin N-demethylation) in the one patient studied. Our identification of inducible P450IIIA4 in enterocytes may in part account for drug interactions characteristic of P450IIIA4 substrates and suggests a strategy for controlling entry into the body of a major class of xenobiotics.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Identification of rifampin-inducible P450IIIA4 (CYP3A4) in human small bowel enterocytes.

et al. 1992

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“…The present in vitro study confirms that ketoconazole is a potent inhibitor of CsA metabolism and, thereby, will cause plasma CsA concentrations to increase when coadministered (Dieperink & Moller, 1982;Ferguson et al, 1982;Cockburn, 1986). It has been suggested that the co-administration of ketoconazole could reduce CsA dosage requirements with consequent cost implications (First et al, 1989(First et al, , 1991, although this has been challenged (Frey, 1990).…”

Section: Discussionmentioning

confidence: 99%

Comparative effects of the antimycotic drugs ketoconazole, fluconazole, itraconazole and terbinafine on the metabolism of cyclosporin by human liver microsomes.

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Tjia

1991

Brit J Clinical Pharma

144

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“…docetaxel (CYP3A4; Marre et al, 1996), etoposide (CYP3A4: Relling et al, 1994) and vinca alkaloids (CYP3A4; Zhou et al, 1993). With this kind of intervention, the inhibition of cyclosporin or etoposide metabolism by ketoconazole has already been used intentionally to reduce the cost of cyclosporin treatment and to improve the bioavailability of oral etoposide (First et al, 1989;Kobayashi et al 1996). Schwartz et al (1995) have successfully used fluconazole to reverse the accelerated trans-retinoic acid clearance in patients with acute promyelocytic leukaemia On the other hand.…”

Section: Discussionmentioning

confidence: 99%

Potent and non-specific inhibition of cytochrome P450 by JM216, a new oral platinum agent

Ando

Shimizu²,

Nakamura³

et al. 1998

Br J Cancer

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Summary Bis-acetato-ammine-dichloro-cyclohexylamine-platinum (IV) (Fukuoka et al. 1991: McGuire et al. 1996. These agents available today are. however, generally administered intravenously. The development of an oral platinum drug has been desired to improve the quality of life of patients receiving cancer chemotherapy in terms of easy administration. Bis-acetato-ammine-dichloro-cvclohexylamineplatinum (IV). JM2 16. is the first oral antineoplastic platinum agent currently under development. In preclinical studies. JM' 16 exhibited in vitro and in vivo anti-tumour efficacy comparable with cisplatin and carboplatin. and an activity against cell lines that were resistant to cisplatin (Kelland et al. 1993). Several phase H clinical trials of JM216 monotherapy have already been performed in the United States and Europe. and a phase I study has finished in Japan (Groen et al. 1996: Fujii et al. 1997: Peereboom et al. 1997. Further, some combination regimens of JM216 with other anti-tumour agents. such as taxans. can be expected. but no information on the potential dru2 interactions bet-een JM2 16 and other drugs has been reported.The metabolic pathway of the drug is complicated and has not been well understood (Raynaud et al. 1996). However, there are some implications that metabolism of JM216 might affect drugmetabolizing enzymes in the liver. First. at least six metabolites were detected in plasma samples from patients who received JM216 (Raynaud et al. 1996). Four of them were also obtained by in mvitro incubations with fresh human plasma. whereas the

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Concomitant Administration of Cyclosporin and Ketoconazole in Renal Transplant Recipients

Cited by 73 publications

References 8 publications

Identification of rifampin-inducible P450IIIA4 (CYP3A4) in human small bowel enterocytes.

Identification of rifampin-inducible P450IIIA4 (CYP3A4) in human small bowel enterocytes.

Comparative effects of the antimycotic drugs ketoconazole, fluconazole, itraconazole and terbinafine on the metabolism of cyclosporin by human liver microsomes.

Potent and non-specific inhibition of cytochrome P450 by JM216, a new oral platinum agent

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