Pharmacokinetic variability of clarithromycin and differences in CYP3A4 activity in patients with cystic fibrosis.

Article Details

Citation

Copy to clipboard

Dalboge CS, Nielsen XC, Dalhoff K, Alffenaar JW, Duno M, Buchard A, Uges DR, Jensen AG, Jurgens G, Pressler T, Johansen HK, Hoiby N

Pharmacokinetic variability of clarithromycin and differences in CYP3A4 activity in patients with cystic fibrosis.

J Cyst Fibros. 2014 Mar;13(2):179-85. doi: 10.1016/j.jcf.2013.08.008. Epub 2013 Sep 10.

PubMed ID

24035278 [ View in PubMed

]

Abstract

BACKGROUND: To investigate the correlation between CYP3A4/5 activity and clarithromycin metabolism, and between CYP3A activity and CYP3A genotype. METHODS: This is an open-label, prospective pharmacokinetic study evaluating CYP3A activity using The Erythromycin Breath Test. Eight blood samples were collected within 12h after clarithromycin 500 mg was administered orally. The clarithromycin concentrations were measured by liquid chromatography-tandem mass spectrometry. AUC, Tmax and Cmax were calculated. Selected Single Nucleotide polymorphisms in CYP3A4/5 genes were assessed by PCR and single base extension. RESULTS: Twenty-one chronically infected patients were included. An 8-fold variation in the CYP3A4 activity, 10-fold variation in AUC for clarithromycin (median 881 mug/mL x min), and a 16-fold variation in Cmax for clarithromycin (median 3.4 mug/mL) were found. A linear correlation between the CYP3A4-activity and clarithromycin metabolism was demonstrated (P < 0.05). CONCLUSION: The large variation in the clarithromycin pharmacokinetics in cystic fibrosis patients may cause treatment failure. The Erythromycin Breath Test could be valuable in identifying cystic fibrosis patients in risk of treatment failure/drug toxicity.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Clarithromycin	Cytochrome P450 3A4	Protein	Humans	Unknown	Substrate Inhibitor	Details