Amphotericin B-induced seizures in a patient with AIDS.

OBJECTIVE: To report a case of multiple episodes of seizure activity in an AIDS patent following amphotericin B infusion. CASE SUMMARY: A 46-year-old African-American man experienced recurrent grand mal seizures during intravenous infusion of amphotericin B, then petit mal seizures as the infusion was stopped and the drug concentrations decreased with time. The patients concurrent medications included didanosine, hydroxyzine, promethazine, hydrocortisone, and prochlorperazine. Despite administration of phenytoin and lorazepam, the seizures persisted and occurred only during amphotercin B administration. DISCUSSION: AIDS and cryptococcal meningitis, both of which the patient had, can potentially cause seizures. The patient had a history of alcohol abuse; alcohol intake as well as withdrawal can also cause seizures. Didanosine also has a potential for inducing seizures. However, these other potential causes of seizure were ruled out. The time course of events suggested that amphotericin B was the cause of the seizures in this AIDS patient. CONCLUSIONS: Amphotericin B seems to be the probable cause of the seizures. To date, only three cases of seizures associated with amphotericin B have been reported in the literature, but healthcare providers should be aware of the potential for this rare adverse effect.

Steady state pharmacokinetics of propranolol in Saudi Arabian patients and comparison with data for different populations.

The steady state pharmacokinetics of propranolol was examined in 48 Saudi Arabian patients chronically treated with oral doses [mean (SEM) = 85.8 (5) mg] of this drug. The mean (SEM) of the steady state concentration (Css) per mg/kg daily dose was 21.8 (3.1) ng.ml-1/mg.kg-1. A 6-fold variability in Css was observed between patients treated with 40 mg every 8 hours and 14-fold between patients treated with 40 mg twice daily. The frequency distribution of the apparent oral clearance (TCLor) of propranolol was bimodal with 88% of the patients showing TCLor of 18 to 372 l.hr-1 while the remainder had TCLor of 471 to 749 l.hr-1. The mean (SEM) of the TCLor per kg body weight for all 48 patients was 3.16 (0.38) l.hr-1.kg-1. Both Css and TCLor obtained for Saudi Arabian patients are not significantly different from those reported for subjects from Western populations. While Css increased proportionally (P less than .001) with dosing, a near-significant (P less than .06), inverse, linear relationship was found between age and TCLor. No significant effect of sex, body weight, or disease state (i.e., heart diseases, hypertension, depression, migraine) on Css or TCLor was detected.

Direct, simultaneous measurement of chloramphenicol and its monosuccinate ester in micro-samples of plasma by radial-compression liquid chromatography.

A simple method of simultaneous analysis for chloramphenicol and chloramphenicol succinate in 10-microL samples of plasma is described. We injected the plasma samples directly into a radial-compression liquid chromatograph equipped with a precolumn module and a C18 insert. A mixture of acetic acid solution (pH 3)/acetonitrile (75/25, by vol) was used as mobile phase, at a flow rate of 4 mL/min. We separated the compounds in a 10-micron (particle size) C18 cartridge with a radial compression separation system and detected them in the effluent at 280 nm. The peak height for both compounds was linearly (r greater than 0.9993) related to concentration over the range investigated, 1-50 mg/L. We also performed the analysis with use of an internal standard (methylprednisolone) and obtained equally good results (r greater than 0.9995). We observed no interference from other antibiotics or drugs in the assay, and the inter- and intra-run precision at different concentrations was good (CV, 0 to 5.6%). We analyzed microsamples of plasma from an infant treated for meningitis with chloramphenicol sodium succinate intravenously. Total analysis time for each sample was less than 8 min.