Penile absorption of EMLA cream in piglets: implications for use of EMLA in neonatal circumcision.
EMLA (eutectic mixture of lidocaine and prilocaine) cream is currently not recommended for use in infants < 1 month of age because of the potential risk of methemoglobinemia as a result of the o-toluidine metabolite of prilocaine. We studied bioavailability and changes in methemoglobin levels following topical penile exposure to 1 g of EMLA cream for 1 hour in piglets. Lidocaine, prilocaine, and o-toluidine concentrations were measured simultaneously using a high-performance liquid chromatography method. The systemic bioavailability of EMLA was low: 4.0 +/- (SD) 4.7% for lidocaine (range 0-13.6; n = 8) and 7.2 +/- 5.7% for prilocaine (range 0-14.5; n = 8). The ratio between exposure to o-toluidine with EMLA versus intravenous administration (i.e., AUCEMLA/AUCIV; see text) was also low: 4.2 +/- 9.3% (range 0-28.6; n = 9). The mean maximum methemoglobin value after intravenous administration was 1.23 +/- 0.64% (range 0.5-3.0; n = 12) and after penile application 0.99 +/- 0.36% (range 0.5-2.0; n = 12). The methemoglobin value was elevated significantly above baseline after intravenous administration (p = 0.03), but not after penile application of EMLA. These findings suggest that penile administration of 1 g of EMLA may be safe for neonatal circumcision, but further study is required.
Gazarian
M
M
Division of Clinical Pharmacology and Toxicology, Hospital for Sick Children, Toronto, Ont., Canada.
Taddio
A
A
Klein
J
J
Kent
G
G
Koren
G
G
D000042:Absorption; D000779:Anesthetics, Local / Q000493:pharmacokinetics; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D002944:Circumcision, Male; D018592:Cross-Over Studies; D004338:Drug Combinations; D007275:Injections, Intravenous; D008012:Lidocaine / Q000493:pharmacokinetics*; D000077442:Lidocaine, Prilocaine Drug Combination; D008297:Male; D008708:Methemoglobinemia / Q000097:blood; D009824:Ointments / Q000493:pharmacokinetics; D010413:Penis / Q000378:metabolism*; D011318:Prilocaine / Q000493:pharmacokinetics*; D013552:Swine; D014052:Toluidines / Q000378:metabolism
D000779:Anesthetics, Local; D004338:Drug Combinations; D000077442:Lidocaine, Prilocaine Drug Combination; D009824:Ointments; D014052:Toluidines; D011318:Prilocaine; D008012:Lidocaine; C023622:2-toluidine