What CYP (Cytochrome P450) enzymes metabolize valacyclovir and ciprofloxacin?

CYP Enzyme Metabolism of Valacyclovir and Ciprofloxacin

Valacyclovir

Valacyclovir and its active metabolite acyclovir are NOT metabolized by cytochrome P450 enzymes. 1

• Valacyclovir is rapidly converted to acyclovir and L-valine by first-pass intestinal and/or hepatic metabolism through non-CYP pathways 1
• Acyclovir is converted to inactive metabolites by aldehyde oxidase and by alcohol and aldehyde dehydrogenase, not by CYP enzymes 1
• The FDA label explicitly states: "Neither valacyclovir nor acyclovir is metabolized by cytochrome P450 enzymes" 1
• This lack of CYP metabolism means valacyclovir has minimal potential for CYP-mediated drug-drug interactions 1

Ciprofloxacin

Ciprofloxacin is NOT a substrate of CYP enzymes but acts as an inhibitor of CYP1A2. 2

Metabolism Profile

• Ciprofloxacin undergoes minimal hepatic metabolism, with approximately 15% of an oral dose converted to metabolites in human urine 2
• The primary route of elimination is renal excretion, with 40-50% of an oral dose excreted unchanged in urine 2
• Ciprofloxacin is not metabolized by CYP enzymes but instead inhibits them 2

CYP1A2 Inhibition

• Ciprofloxacin is an inhibitor of human cytochrome P450 1A2 (CYP1A2) mediated metabolism 2
• Co-administration with drugs primarily metabolized by CYP1A2 results in increased plasma concentrations of those drugs and could lead to clinically significant adverse events 2
• Research confirms ciprofloxacin significantly inhibits CYP1A2 activity, with competitive inhibition demonstrated in microsomal studies (Ki = 2.0 mM) 3
• Ciprofloxacin also inhibits CYP3A4-mediated metabolism, though to a lesser extent than CYP1A2, with competitive inhibition of erythromycin N-demethylation demonstrated in both human and rat microsomes 3

Clinical Implications

• The CYP1A2 inhibition by ciprofloxacin can increase plasma concentrations of drugs like theophylline, caffeine, tizanidine, and carbamazepine when co-administered 2, 4
• A clinical study demonstrated that ciprofloxacin significantly increased carbamazepine plasma concentrations (increased Cmax and AUC, decreased clearance) when given concurrently, likely through CYP3A4 inhibition 4
• Dose adjustment and therapeutic drug monitoring may be required when ciprofloxacin is given with CYP1A2 substrates 4