In vitro interaction between cyclosporin A and macrolide antibiotics [letter]

Marre, F; Sousa, Georges de; Orloff, A M; Rahmani, Roger

doi:10.1111/j.1365-2125.1993.tb04166.x

Cited by 10 publications

(3 citation statements)

References 8 publications

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“…The CsA pharmacokinetic variability is hard to manage for clinicians, since many factors have been described to influence CsA blood concentrations 3,7,28,29,49–51 . In our cohort, one‐third of patients reached this therapeutic window a few days after HSCT.…”

Section: Discussionmentioning

confidence: 92%

A Clinical Decision Support Tool to Find the Best Initial Intravenous Cyclosporine Regimen in Pediatric Hematopoietic Stem Cell Transplantation

Leclerc

Ducher

Ceraulo

et al. 2021

The Journal of Clinical Pharma

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To optimize cyclosporine A (CsA) dosing regimen in pediatric patients undergoing hematopoietic stem cell transplantation (HSCT), we aimed to provide clinicians with a validated decision support tool for determining the most suitable first dose of intravenous CsA. We used a 10‐year monocentric data set of pediatric patients undergoing HSCT. Discretization of all variables was performed according to literature or thanks to algorithms using Shannon entropy (from information theory) or equal width intervals. The first 8 years were used to build the Bayesian network model. This model underwent a 10‐fold cross‐validation, and then a prospective validation with data of the last 2 years. There were 3.3% and 4.1% of missing values in the training and the validation data set, respectively. After prospective validation, the Tree‐Augmented Naïve Bayesian network shows interesting prediction performances with an average area under the receiver operating characteristic curve of 0.804, 32.8% of misclassified patients, a true‐positive rate of 0.672, and a false‐positive rate of 0.285. This validated model allows good predictions to propose an optimized and personalized initial CsA dose for pediatric patients undergoing HSCT. The clinical impact of its use should be further evaluated.

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Section: Discussionmentioning

confidence: 92%

A Clinical Decision Support Tool to Find the Best Initial Intravenous Cyclosporine Regimen in Pediatric Hematopoietic Stem Cell Transplantation

Leclerc

Ducher

Ceraulo

et al. 2021

The Journal of Clinical Pharma

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“…The current in-vitro study also showed that rokitamycin is a poor inhibitor of 3hydroxylation of quinine, a substrate of CYP3A (Zhao & Ishizaki 1997), by rat liver microsomes, 1172 XUE-JUN ZHAO AND TAKASHI ISHIZAKI which is consistent with a recent study by Tsuruta et al (1997) who reported that rokitamycin, both invitro and in-vivo, had little inhibitory effect on the metabolism of nifedipine, another substrate for CYP3A (Guengerich et al 1986) in rats. However, two in-vitro studies with liver microsomes from man revealed that rokitamycin inhibited the CYP3A-mediated metabolism of cyclosporin (Marre et al 1993) and triazolam (Zhao et al 1999) with mean Ki (IC50) values of 30 and 2Á0 ( AE 5Á8) mM, respectively. These data are not in accord with our current ®nding that rokitamycin inhibited CYP3A-mediated quinine 3-hydroxylation only weaklyÐmean IC50 b 100 mM in microsomal samples obtained from three different rat livers (Table 2).…”

Section: Discussionmentioning

confidence: 99%

An In-vitro Study on the Metabolism of Rokitamycin and Possible Interactions of the Drug with Rat Liver Microsomes

Zhao

Ishizaki

1999

Journal of Pharmacy and Pharmacology

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This in-vitro study was designed to identify the enzyme(s) involved in the major metabolic pathway of rokitamycin, i.e. the formation of leucomycin A7, and to assess possible interactions of the drug with rat liver microsomes. Formation of leucomycin A7 was NADPH-independent and was not appreciably inhibited by anti-rat NADPH cytochrome P-450 reductase serum or cimetidine, a nonspecific inhibitor of cytochrome P-450 isoforms. Eadie-Hofstee plots for the formation of leucomycin A7 were indicative of apparently monophasic behaviour for six rat liver microsomes tested. The mean (+/- s.d.) kinetic parameters, Km, Vmax and Vmax/Km, for the formation of leucomycin A7 from rokitamycin were 47+/-13 microM, 390+/-56 nmol min(-1) (mg protein)(-1) and 8.6+/-1.6 mL min(-1) (mg protein)(-1), respectively. Three esterase inhibitors (100 microM), bis-nitrophenylphosphate, physostigmine and metrifonate inhibited the formation of leucomycin A7 by more than 60%. Metabolism of rokitamycin was inhibited by terfenadine, but not by mequitazine, whereas chlorpheniramine and theophylline activated the formation of leucomycin A7. Rokitamycin, leucomycin A7, leucomycin V, erythromycin and clarithromycin were weak inhibitors of CYP3A-catalysed 3-hydroxylation of quinine with mean IC50 values ranging from 71 to >100 microM. It is concluded that in rat liver microsomes the formation of leucomycin A7 from rokitamycin is catalysed mainly by an esterase (possibly cholinesterase, EC3.1.1.8), but not by cytochrome P-450 enzyme(s). Although in this in-vitro animal study CYP3A activity was barely inhibited by rokitamycin, the possibility cannot be totally discounted in man when rokitamycin is co-administered with drugs metabolized by CYP3A.

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“…Cardiotoxicity may be manifested by an increase in the U-waves and the development of Torsade de Pointes ventricular arrhythmias brought about by altered cardiac repolarization (QT prolongation) [11][12][13][14][15]. Ketoconazole and erythromycin are potent inhibitors of human liver microsomal CYP3A [16].…”

Section: Introductionmentioning

confidence: 99%

The pharmacokinetic and pharmacodynamic interaction between zileuton and terfenadine

Awni¹,

Cavanaugh²,

Leese³

et al. 1997

European Journal of Clinical Pharmacology

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In vitro interaction between cyclosporin A and macrolide antibiotics [letter]

Cited by 10 publications

References 8 publications

A Clinical Decision Support Tool to Find the Best Initial Intravenous Cyclosporine Regimen in Pediatric Hematopoietic Stem Cell Transplantation

A Clinical Decision Support Tool to Find the Best Initial Intravenous Cyclosporine Regimen in Pediatric Hematopoietic Stem Cell Transplantation

An In-vitro Study on the Metabolism of Rokitamycin and Possible Interactions of the Drug with Rat Liver Microsomes

The pharmacokinetic and pharmacodynamic interaction between zileuton and terfenadine

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