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PI‐60
Author(s) -
Nolin T. D.,
Appiah K.,
Kendrick S. A.,
Le P.,
McMonagle E.,
Himmelfarb J.
Publication year - 2006
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2005.12.081
Subject(s) - hemodialysis , cyp3a4 , medicine , pharmacology , metabolism , cytochrome p450
BACKGROUND Altered drug metabolism has been demonstrated in patients with end‐stage renal disease (ESRD). The aim of this study was to evaluate the acute effect of hemodialysis (HD) on CYP3A4 activity. METHODS 12 ESRD patients undergoing chronic HD and 12 matched control subjects participated. Hepatic CYP3A4 activity was assessed using the 14 C‐erythromycin breath test (EBT). The EBT was administered two hours pre‐ and repeated two hours post‐hemodialysis and once in controls. Breath samples were collected at baseline and various time points up to 120 min after dosing, and then analyzed for 14 C using scintillation counting. The traditional 20‐min flux measure and the novel 1/Tmax parameter were determined. RESULTS The flux of 14 CO 2 at the 20‐minute time point, expressed as the % of the administered dose exhaled per hour, increased by 27% post‐dialysis, from 2.34±0.8 to 2.98±1.04 (p<0.05). Pre‐ and post‐HD values were similar to those observed in control subjects (2.70±0.59; p=NS). Pre‐ and post‐HD 1/Tmax values approached but did not achieve a statistically significance difference (0.056±0.01 and 0.067±0.02, respectively, p=0.07). Pre‐HD 1/Tmax was lower than control (0.064±0.01, p<0.05) and normalized after dialysis. CONCLUSIONS These results suggest that hemodialysis acutely improves hepatic CYP3A4 activity and indicate that increased diligence is warranted when prescribing CYP3A substrates to ESRD patients. Clinical Pharmacology & Therapeutics (2005) 79 , P23–P23; doi: 10.1016/j.clpt.2005.12.081