Pharmacokinetics and absorption of paromomycin and gentamicin from topical creams used to treat cutaneous leishmaniasis
| Autor: | Yuh-Jing Lin, Nestor Sosa, William R. Ravis, Alejandro Llanos-Cuentas, Carl J. Nielsen, Philip L. Smith, Kirsten S. Smith, Karen M. Kopydlowski, Mara Kreishman-Deitrick, Janet Ransom, Max Grogl |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Adult
Male double blind procedure area under the curve Paromomycin Cmax Leishmaniasis Cutaneous Pharmacology gentamicin Clinical Therapeutics cream Cutaneous leishmaniasis Pharmacokinetics purl.org/pe-repo/ocde/ford#3.02.21 [https] parasitic diseases medicine Humans Pharmacology (medical) controlled study human Child plasma drug accumulation skin leishmaniasis drug absorption business.industry maximum plasma concentration Leishmaniasis medicine.disease time to maximum plasma concentration carbohydrates (lipids) Infectious Diseases Visceral leishmaniasis isomer Toxicity randomized controlled trial Gentamicin Female Gentamicins business medicine.drug |
| Zdroj: | Antimicrobial agents and chemotherapy. 57(10) |
| ISSN: | 1098-6596 |
| Popis: | 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 (AUC 0–24 ) 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 AUC 0–24 and maximum concentration of drug ( C max ) were 5 to 6 times greater than those on day 1 for both treatment groups. For the paromomycin-alone group, the AUC 0–24 was 8,575 ± 7,268 ng · h/ml and the C max 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 AUC 0–24 or C max 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.) |
| Databáze: | OpenAIRE |
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