This study evaluated the pharmacokinetics of topical creams containing 15%
paromomycin ("
paromomycin alone") and 15%
paromomycin plus 0.5%
gentamicin (WR 279,396) in patients with
cutaneous leishmaniasis. The investigational creams were applied topically to all lesions once daily for 20 days. Plasma samples were analyzed for simultaneous quantitation of
paromomycin and
gentamicin isomers and total
gentamicin. Pharmacokinetic parameters for
gentamicin could not be calculated because detectable levels were rarely evident. After one application, the
paromomycin area under the concentration-time curve from 0 to 24 h (AUC0-24) was 2,180 ± 2,621 ng · h/ml (mean ± standard deviation [SD]) for the
paromomycin-alone group and 975.6 ± 1,078 ng · h/ml for the WR 279,396 group. After 20 days of application, the
paromomycin AUC0-24 and maximum concentration of drug (Cmax) were 5 to 6 times greater than those on day 1 for both treatment groups. For the
paromomycin-alone group, the AUC0-24 was 8,575 ± 7,268 ng · h/ml and the Cmax was 1,000 ± 750 ng/ml, compared with 6,037 ± 3,956 ng · h/ml and 660 ± 486 ng/ml for the WR 279,396 group, respectively. Possibly due to large intersubject variability, no differences (P ≥ 0.05) in the AUC0-24 or Cmax were noted between treatment or between sites on day 1 or 20. The percentage of dose absorbed on day 20 was 12.0% ± 6.26% and 9.68% ± 6.05% for
paromomycin alone and WR 279,396, respectively.
Paromomycin concentrations in plasma after 20 days of application were 5 to 9% of those after intramuscular administration of 15 mg/kg of
body weight/day to adults for the systemic treatment of
visceral leishmaniasis. Effective topical treatment of
cutaneous leishmaniasis appears to be possible with limited
paromomycin and
gentamicin systemic absorption, thus avoiding drug accumulation and toxicity. (The work described here has been registered at ClinicalTrials.gov under registration no. NCT01032382 and NCT01083576.).