Biomedical subjects
J G Gambertoglio
Publications and source records attributed to J G Gambertoglio.
Removal of phenytoin by hemodialysis in uremic patients.
The removal of phenytoin by hemodialysis was determined in seven uremic patients. Four patients were receiving phenytoin sodium for therapeutic purposes; three received one dose each intravenously to quantitate its disposition in uremia. The drug was measured in whole blood, plasma, saliva, and dialysate. Only 2% to 4% of the intravenous dose was recovered in the dialysate. Phenytoin clearance by dialysis was 7 to 14 ml/min; plasma clearance was 53 to 133 ml/min. Since hemodialysis contributes little toward shortening to 11-to-18-hour half-life of phenytoin in the uremic patients, no supplemental dose is necessary for uremic patients undergoing hemodialysis.
Kinetics of oral ethambutol in the normal subject.
Six normal adult volunteers received 15 mg/kg of ethambutol (EMB) by mouth, once as an aqueous solution and again as the commercial tablet preparation. Each dose was separated by at least 7 days. Plasma and urine samples were collected at regular intervals for up to 24 and 72 hr, respectively. Peak plasma concentrations ranged from 3.25 to 5.62 mcg/ml, 2 to 4 hr after tablet dosage. Earlier peak times were found after administering the solution. For plasma concentrations up to 12 hr there was a distinct distribution phase followed by an apparent elimination phase with a mean half-life (t 1/2) (+/- SD) of 4.06 +/- 0.53 and 4.78 +/- 0.41 hr for the tablet and the solution, respectively. Excretion rate plots exhibited similar t 1/2 values for the apparent elimination phase. An even longer t 1/2 of approximately 10 hr was evident from 24-hr plasma samples and urinary excretion measurements up to 72 hr. Unchanged drug excreted in the urine averaged 61.1 +/- 3.8% of the dose for the tablet and 63.4 +/- 2.6% for the solution. Plasma protein binding for ethambutol determined by equilibrium dialysis and ultrafiltration was approximately 20% to 30%. The concentration ratio of ethambutol in erythrocytes to plasma ranged from 1.1 to 1.6.
Hemodialysis of phenytoin in a uremic patient.
Removal of phenytoin by hemodialysis was determined in a uremic patient. The rate of appearance of the drug in dialysate, the plasma concentration with time, and the plasma clearance by dialysis were measured. Plasma protein binding of phenytoin was also determined. In spite of greatly reduced plasma protein binding in the uremic patient, removal rate was observed to be less than 10% of the rate of presentation of the dialyzer. During the 6-hr period of dialysis, the plasma concentration showed little change. The amount collected in the dialyase, 43.6 mg, was only a small fraction of drug in the body. These results indicate that replacement of phenytoin based on the amount of drug removed by dialysis is unnecessary in chronically dialyzed uremic patients. In addition, the utility of hemodialysis in phenytoin overdose is questioned.
Acute massive chloral hydrate intoxication treated with hemodialysis: a clinical pharmacokinetic analysis.
A 38-year-old female became comatose and exhibited signs of cardiac toxicity 2 hours after ingestion of approximately 38 Gm chloral hydrate. Hemodialysis was initiated 21 hours after ingestion, using twin coils in series, and was continued for 4.5 hours. Trichloroethanol, the active metabolite of chloral hydrate, was measured in plasma and dialysate. Two hours after ingestion, the plasma level was 330 micrograms/ml (average therapeutic level is 12 micrograms/ml or less). The predialysis level was 216 micrograms/ml and after dialysis declined to 141 micrograms/ml. The pre- and post-plasma half-life values were 35 hours, while on dialysis the half-life was only 6 hours. The average dialysis clearance was 120 ml/minute, and the amount of chloral hydrate removed by dialysis was 5.79 Gm. By the end of dialysis, the patient could respond to verbal commands and was ambulatory 36 hours later. In conclusion, hemodialysis can be a clinically important method of treating chloral hydrate overdose.
Pharmacokinetic disposition of cefonicid in patients with renal failure and receiving hemodialysis.
Cefonicid is a new cephalosporin with a spectrum of activity similar to that of cefamandole. The pharmacokinetic disposition of the drug was examined in patients with various degrees of renal dysfunction and who were receiving hemodialysis. After patients were given a 7.5 mg/kg dose as an iv infusion, multiple blood and urine samples were obtained at frequent intervals, and the samples were analyzed for cefonicid concentration. Five patients receiving hemodialysis received an additional dose before a dialysis period to assess removal of the drug. The half-life of cefonicid increased markedly with declining renal function (approximately 70 hr in anuric patients). Total clearance and renal clearance decreased linearly with decreases in creatinine clearance. Steady-state volume of distribution remained approximately the same (0.11 liter/kg) in all patients. Cefonicid dosage can be reduced in proportion to decreases in creatinine clearance from normal levels. A simple nomogram is provided.