Oral trimethoprim-sulphamethoxazole levels in stable HIV-infected children.
BACKGROUND
Effective treatment of Pneumocystis jiroveci pneumonia (PCP) requires therapeutic serum concentrations of 5-10 microg/ml trimethoprim (TMP); consequently intravenous trimethoprim-sulphamethoxazole (TMP-SMZ) is recommended therapy. However, oral therapy is desirable as the intravenous route is costly, time-consuming, more difficult to administer and carries a risk of needlestick injury.


OBJECTIVE
To investigate whether therapeutic TMP levels for treatment of PCP can be attained with oral therapy in HIV-infected children.


METHODS
A prospective dose-escalation study was undertaken of serum TMP levels attained following oral doses of TMP of 5 mg/kg, 10 mg/kg or 20 mg/kg in stable HIV-infected children. Children who received a 20 mg/kg dose were randomised to get a second dose (5 or 10 mg/kg TMP) at 6 hours. TMP levels were measured at baseline, peak (3 hours), and trough (6 hours) using liquid chromatography. An additional TMP level was taken at 9 hours in those who received a second TMP dose.


RESULTS
Median (25th-75th percentile) peak serum TMP levels following a 5 mg/kg, 10 mg/kg or 20 mg/kg oral loading dose were 0.93 (0.5-1.5) microg/ml, 1.94 (1.4-2.2) microg/ml and 7.68 (6.1-7.8) microg/ml respectively. Peak TMP levels at 9 hours after a second TMP dose of 5 or 10 mg/kg were 6.98 (3.4-8.8) microg/ml and 9.25 (8.2-10.3) microg/ml respectively.


CONCLUSIONS
Therapeutic concentrations of TMP for treatment of P. jiroveci can be attained with an oral loading dose of 20 mg/kg and sustained with a second dose at 6 hours of either 5 mg or 10 mg/kg in stable HIV-infected children.
Zar
Heather J
HJ
School of Child and Adolescent Health, Red Cross War Memorial Children's Hospital, Cape Town. hzar@ich.uct.ac.za
Langdon
Grant
G
Apolles
Patti
P
Eley
Brian
B
Hussey
Gregory
G
Smith
Peter
P
D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy*; D000284:Administration, Oral; D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D045363:Pneumocystis carinii / Q000187:drug effects; D011020:Pneumonia, Pneumocystis / Q000188:drug therapy*; D011446:Prospective Studies; D016896:Treatment Outcome; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000008:administration & dosage* / Q000493:pharmacokinetics*
D000890:Anti-Infective Agents; D015662:Trimethoprim, Sulfamethoxazole Drug Combination