Clinical usefulness of high-pressure liquid chromatographic determination of serum pentamidine in AIDS patients.
We have developed a reproducible HPLC method to determine serum pentamidine, which demonstrates good chromatographic performance, and is sensitive enough to measure therapeutic doses. Pentamidine is first extracted from serum by passage through a C-18 extraction cartridge. Potential interfering substances are then removed by washing with 100% methanol. Pentamidine is eluted from the extraction cartridge with 1-heptanesulfonic acid. The extract is chromatographed on a highly deactivated column for basic compounds in the presence of minimal concentrations of 1-heptanesulfonic acid as the pairing agent. Detection is by fluorescence. The method can determine serum pentamidine levels in the range of 15-600 ng/mL free of interference from other drugs. In monitoring pentamidine levels in AIDS patients with Pneumocystis carinii, we found that trough serum levels over 100 ng/mL were associated with toxicity (hypoglycemia or azotemia) in 100% of patients. With levels under 100 ng/mL, signs of toxicity were observed in only 29% of the patients. We conclude that dose adjustment based on serum levels reduces the incidence of toxicity and enhances pentamidine therapy.
Vinet
B
B
Biochemistry, Department, Hôpital Notre-Dame, Montréal, Québec, Canada.
Comtois
R
R
Gervais
A
A
Lemieux
C
C
D000163:Acquired Immunodeficiency Syndrome / Q000097:blood* / Q000150:complications; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D016903:Drug Monitoring; D005069:Evaluation Studies as Topic; D006801:Humans; D010419:Pentamidine / Q000009:adverse effects / Q000097:blood* / Q000627:therapeutic use; D011020:Pneumonia, Pneumocystis / Q000097:blood* / Q000150:complications / Q000188:drug therapy
D010419:Pentamidine