G04BD04 - Oxybutynin |
Propably not porphyrinogenic |
PNP |
Rationale
Oxybutynin is not an inducer or mechanism-based inhibitor of any major CYP enzymes, and therefore no pharmacokinetic porphyrinogenic effects are suspected.
Therapeutic characteristics
Oxybutynin is an anticholinergic spasmolytic used in the treatment of urinary incontinence, urgency and frequency in unstable bladder conditions. It may also be used in the treatment of hyperhidrosis.
It may be administered by the oral, rectal, transdermal or intravesical route.
Metabolism and pharmakokinetics
Oxybutynin is metabolized primarily by CYP3A4. It undergoes extensive first pass gastric and hepatic metabolism and the bioavailability of oxybutynin from orally administered preparations is about 6 %. The plasma level of the pharmacologically active metabolite, desethyloxybutynin, is about 5 to 12 times greater than oxybutynin following oral ingestion (Kennelly 2010 FDA label, SPC). The half-life of oxybutynin is approximately 2 to 3 hours.
In an in vitro study oxybutynin was found not to inhibit major human CYPs at clinically relevant concentrations. This study also concluded that oxybutynin is not a time-dependent inhibitor. (Dahlinger 2017).
In another in vitro study it was observed a 50% reduction in CYP3A4 activity at oxybutynin concentrations that might theoretically occur in the gut wall from orally administered preparations (Lukkari 1998).
IPNet drug reports
Uneventful use reported in 3 patients with acute porphyria.
References
- Scientific articles
- Dahlinger D, Aslan S. Assessment of inhibitory effects on major human cytochrome P450 enzymes by spasmolytics used in the treatment of overactive bladder syndrome. Ther Adv Urol. 2017 Jul; 9(7): 163-177. PMID 28747995. #4478
- Kennelly MJ. A Comparative Review of Oxybutynin Chloride Formulations: Pharmacokinetics and Therapeutic Efficacy in Overactive Bladder Rev Urol. 2010 Winter; 12(1): 12-19. PMID 20428289. #1545
- Lukkari E, Taavitsainen P, Juhakoskr A, et al. Cytochrome P450 specificity of metabolism and interactions of oxybutynin in human liver microsomes. Pharmacol Toxicol 1998; 82: 161-66. PMID 9584328. #4479
- Government bodies
- U.S. Food and Drug Administration (FDA). Label information. Ditropan. (Revised: 2011). #1547
- Summary of Product Characteristics
- The electronic Medicines Compendium (emc). Summary of Product Characteristics (SPC). Oxybutynin hydrochloride. #1546
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