+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

Optimal dosing of miltefosine in children and adults with visceral leishmaniasis

, : Optimal dosing of miltefosine in children and adults with visceral leishmaniasis. Antimicrobial Agents and ChemoTherapy 56(7): 3864-3872

Only anecdotal data are available on the pharmacokinetics (PK) of miltefosine in children suffering from visceral leishmaniasis (VL). While failure rates were higher in children with VL, steady-state concentrations appeared lower than those seen with adults. We hypothesized that the current linear dosage (in milligrams per kilogram of body weight) is too low for children and that a new dosing algorithm based on an appropriate body size model would result in an optimal exposure. A population PK analysis was performed on three historic pooled data sets, including Indian children, Indian adults, and European adults. Linear and allometric scaling of PK parameters by either body weight or fat-free mass (FFM) was evaluated for body size models. Based on the developed PK model, a dosing algorithm for miltefosine in children and adults was proposed and evaluated in silico. The population PK model employing allometric scaling fitted best to the pooled miltefosine data. Allometric scaling by FFM reduced between-subject variability, e.g., for drug clearance, from 49.6% to 32.1%. A new allometric miltefosine dosing algorithm was proposed. Exposure to miltefosine was lower in children than adults receiving 2.5 mg/kg/day: a Cmax of 18.8 μg/ml was reached by 9% of adults and 66.7% of children. The allometric daily dose resulted in similar levels of exposure to miltefosine for adults and children. The use of a new allometric dosing algorithm for miltefosine in VL patients results in optimal exposure to miltefosine in both adults and children and might improve clinical outcome in children.


PMID: 22585212

DOI: 10.1128/AAC.00292-12

Other references

Osz, E.; Sos, E.; Somsak, L.; Szilagyi, L.; Dinya, Z., 1997: A straightforward route to hydantocidin analogues with pyranose ring structure. Partial hydrolysis of the nitrile moiety in acetylated 1-bromo-glycopyranosyl cyanides 1 and 9 mediated by TiCl-4 gave C-(1-bromo-1-deoxy-glycopyranosyl)formamides 2 and 10 whose reaction either with AgOCN, AgSCN or KSCN in nitromethane resulted i...

Van Der Velden, V.H.J.; Malec, M.; Van Wering, E.R.; Kardos, G.; Bierings, M.; Hart, P.G.; Porwit Macdonald, A.; Van Dongen, J.J.M.; Revesz, T., 2003: Therapy-related lineages switch in childhood acute leukemia. Leukemia (Basingstoke) 17(3): 673, March

Sansone, P.; Saslaw, M.S.; Hennekens, C.H., 1972: High titer Widal reaction. JAMA 220(12): 1615-1616

Kobayashi, Y.; Shibusawa, A.; Saito, H.; Ohshiro, N.; Ohbayashi, M.; Kohyama, N.; Yamamoto, T., 2005: Isolation and functional characterization of a novel organic solute carrier protein, hOSCP1. We succeeded in isolating a novel organic solute carrier from a human placenta cDNA library. The isolated cDNA consisted of 1137 base pairs that encoded a 379-amino acid protein, hOSCP1. Northern blot and reverse transcription PCR analyses reveale...

Lopes Cardozo, E.; Harting, M.C., 1972: On the function of lymphocytes in malignant effusions. Acta Cytologica 16(4): 307-313

Calmus, Y.; Ayani, E.; Chereau, C.; Kahan, A.; Houssin, D.; Weill, B., 1993: Study of the target antigens of hyperacute xenogeneic rejection in discordant combinations. Transplantation Proceedings 25(1 Pt 1): 379-381

Bellieni, C.V.; Pinto, I.; Bogi, A.; Zoppetti, N.; Andreuccetti, D.; Buonocore, G., 2012: Exposure to electromagnetic fields from laptop use of "laptop" computers. Portable computers are often used at tight contact with the body and therefore are called "laptop." The authors measured electromagnetic fields (EMFs) laptop computers produce and estimated the induced currents in the body, to assess the...

Malon, Aélie.; Deschamps, Vérie.; Salanave, B.; Vernay, M.; Szego, E.; Estaquio, C.; Kesse-Guyot, E.; Hercberg, S.; Castetbon, K., 2010: Compliance with French nutrition and health program recommendations is strongly associated with socioeconomic characteristics in the general adult population. In many countries, nutrition policies such as the Programme National Nutrition Santé (PNNS), implemented in France since 2001, have been developed to prevent and reduce the risk of chronic disease. However, the way in which such programs might be...

Asin, H.M., 1966: Symphalangia of the fifth toes. Journal of the American Podiatry Association 56(9): 411-413

Radha, V.; Jakob, E.K.; Oluf, P.; Mohan, V.; Torben, H., 2003: Identification of novel mutations in the HNF-1alpha gene in south Indian patients with maturity onset diabetes of the young. Diabetes 52(Supplement 1): A254-A255