The measurement of urinary hydroxyurea in sickle cell anaemia.
Hydroxyurea is increasingly used in the treatment of sickle cell disease (SCD) although there is little evidence on how best to monitor treatment and compliance. It is also not known why 10-50% patients do not benefit from the drug and whether some of this resistance is because of pharmacokinetic factors. We have developed an assay using mass spectrometry (MS) to measure urinary concentrations of hydroxyurea. We have used this assay to study 12 children and six adults with SCD taking hydroxyurea and found that urinary hydroxyurea was present for at least 12 h following tablet ingestion. Thirty-five urine samples were analysed that were expected to contain hydroxyurea, based on the reported timing of the last dose and hydroxyurea was detected in 29 (83%) of these. There were also marked differences in urinary hydroxyurea concentrations, suggesting pharmacokinetic variability may explain some of the differences in response to hydroxyurea. Urine samples were also analysed by MS for penicillin metabolites and 43 of the 57 (75%) contained phenoxyacetate, suggesting the ingestion of penicillin within the last 12 h. These assays are potentially useful to study hydroxyurea metabolism further, develop optimal dosing regimes and monitor compliance with treatment.
Dalton
R Neil
RN
Paediatrics, Guy's and St Thomas' NHS Trust, London, UK.
Turner
Charles
C
Dick
Moira
M
Height
Susan E
SE
Awogbade
Moji
M
Inusa
Baba
B
Okpala
Iheanyi
I
O'Driscoll
Sandra
S
Thein
Swee Lay
SL
Rees
David C
DC
D000293:Adolescent; D000755:Anemia, Sickle Cell / Q000188:drug therapy / Q000652:urine*; D000986:Antisickling Agents / Q000627:therapeutic use / Q000652:urine*; D015415:Biomarkers / Q000652:urine; D002648:Child; D003404:Creatinine / Q000652:urine; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use / Q000652:urine*; D008297:Male; D010349:Patient Compliance; D010404:Penicillin V / Q000627:therapeutic use; D010642:Phenoxyacetates / Q000652:urine
D000986:Antisickling Agents; D015415:Biomarkers; D010642:Phenoxyacetates; D003404:Creatinine; D006918:Hydroxyurea; D010404:Penicillin V