Pharmacokinetics of quinine in obesity.

Obesity can modify the pharmacokinetics of lipophilic drugs. As quinine is a lipophilic drug, this study was conducted to determine whether the pharmacokinetics of quinine is altered in obese subjects. Nine obese Thai men were compared with 8 age-matched lean men. After an oral dose of quinine had been given to the men, plasma quinine concentrations were measured up to 48 h after the dosing. Mean peak plasma quinine concentration in the obese group was significantly lower than that observed in the controls (4.0 +/- 0.8 vs 5.0 +/- 0.3 mg/L, P < 0.01). There were no significant differences in time to reach the peak plasma concentration, half-life and total clearance of quinine between the 2 groups. The mean clearances of quinine normalized to the ideal bodyweight (IBW) in the obese and the control groups were not significantly different (0.091 +/- 0.018 vs 0.091 +/- 0.024 L/h/kg IBW, P > 0.05). As there are similarities in the total clearance and the clearance of quinine based on IBW, the maintenance dose of quinine should be given to obese patients on the basis of ideal bodyweight, not on total bodyweight.

Effects of chlorpromazine or diltiazem given intraperitoneally alone or in combination on peritoneal transport of solute and water.

Calcium channel blocker given intraperitoneally (i.p.) in rats was reported to increase urea D/P ratio without protein loss. Chlorpromazine (CP) given i.p. in humans was reported to increase ultrafiltration (UF) and urea clearance. We studied the effects of i.p. Diltiazem (DZ) (15 mg/kg) and i.p. chlorpromazine (0.25 mg/L dialysate)--given alone or in combination--on urea D/P ratio, dialysate protein (Dpro), glucose concentration (Dg), UF, and drainage volume (Vd). Six male Sprague-Dawley rats were studied. The rats underwent 21 consecutive 30-minute exchanges with 15 mL of 1.5% of Dianeal solution (Baxter Healthcare Inc., Deerfield, Illinois, U.S.A.). DZ or CP was added to the dialysis solution during exchanges 4-6 and 10-12. During exchange 16-18 both DZ and CP were added to the dialysis solution. Exchanges 1-3, 7-9, 13-15, and 19-21 were control exchanges performed with 1.5% Dianeal solution alone. The mean weight of the rats was 541.6 +/- 44 g. The animals' blood pressure remained stable during the study period. An increase in D/Purea ratio was observed with DZ, with CP, and with the two drugs in combination, without increase in dialysate protein loss. An increase in UF with a decrease in D/D0 was observed with DZ, with CP, and with the two drugs in combination, suggesting a mechanism other than osmotic gradient--such as increased blood flow or decreased surface tension.

Residual volume in continuous ambulatory peritoneal dialysis patients from various solute calculations.

Residual volume (RV) has been measured using various methods and various solutes. This prospective study set out to determine residual volume by using various solute calculations, and to estimate mean residual volume in stable Thai CAPD patients. Complete data from 9 patients (6 males, 3 females) were analyzed. Residual volume was calculated using various solutes including sodium (Na), potassium (P), glucose (G), urea (U), and creatinine (C). The calculation using sodium was too variable to use to calculate a mean. Mean of residual volume was calculated from the other solutes as RV1 (mean of PUC), RV2 (mean of GUC), and RV3 (mean of PGUC). Mean residual volumes did not correlate with sex, body weight, body surface area, hematocrit, albumin, or membrane characteristics (drained volume). Comparing all means calculated in our study, creatinine was the solute that yielded the most accurate mean, with a correlation coefficient of 0.877, 0.965, and 0.956 for RV1, RV2, and RV3 respectively. In this study, mean residual volumes were 212.49 +/- 100.03 mL, 255.23 +/- 142.58 mL, and 250.42 +/- 121.60 mL for RV1, RV2, and RV3 respectively.

Goodpasture's syndrome superimposed on membranous nephropathy. A case report.

We describe a patient with idiopathic membranous glomerulopathy who developed acute deterioration in renal function; this was associated with hemoptysis, severe hypertension, and anti-glomerular basement membrane (anti-GBM) antibody in the serum. Despite aggressive therapy with plasmapheresis, cyclophosphamide and prednisone, the patient progressed to end-stage renal failure and is on maintenance hemodialysis.

Marked enhancement by rifampicin and lack of effect of isoniazid on the elimination of quinine in man.

The effect of rifampicin and isoniazid pretreatment on the pharmacokinetics of quinine after a single oral dose (600 mg quinine sulphate) was studied in nine healthy young Thai male volunteers using a three-way randomized crossover design. Subjects were studied over three 2 day periods, during which they received no pretreatment, or pretreatment with daily 600 mg p.o. rifampicin for 2 weeks, or isoniazid 300 mg p.o. daily for 1 week, prior to quinine administration. The mean (+/- s.d.) clearance (CL/F) of quinine coadministered with rifampicin (0.87 +/- 0.35 1 h-1 kg-1) was significantly greater than that of quinine alone (0.14 +/- 0.05 1 h-1 kg-1). The mean difference in clearance from the control treatment was 0.73 1 h-1 kg-1, with 95% confidence interval (C.I.) of 0.48 to 0.98. The unbound clearance (CLu/F) of quinine, which reflects the activity of the drug-metabolizing enzymes, was considerably greater (6.9-fold) in subjects when rifampicin was coadministered with quinine than that of quinine alone (6.9 +/- 3.6 vs 1.0 +/- 0.5 1 h-1 kg-1; the 95% C.I. for the mean difference was 3.3 to 8.5). The mean elimination half-life of quinine when coadministered with rifampicin (5.5 +/- 3.0 h) was significantly shorter than when quinine was given alone (11.1 +/- 3.0 h; the 95% C.I. for the mean difference was -8.6 to -2.6). In contrast to rifampicin, pretreatment for 1 week with 300 mg oral isoniazid had no significant effects on the pharmacokinetics of quinine.(ABSTRACT TRUNCATED AT 250 WORDS)

Cigarette smoking enhances the elimination of quinine.

The pharmacokinetics of a single dose (600 mg) of quinine sulphate were examined in a group of non-smokers (n = 10) and in heavy cigarette smokers (n = 10). The mean (+/- s.d.) oral clearance of quinine in smokers (0.189 +/- 0.075 1 h(-1) kg(-1)) was significantly greater than in non-smokers (0.107 +/- 0.045 1 h(-1) kg(-1) , P < 0.01). The unbound clearance of quinine which reflects activity of the drug-metabolizing enzyme, was considerably greater (1.5-fold) in the smokers than in the non-smoker subjects. The mean elimination half-life of quinine in smokers was 7.5 +/- 1.4 (s.d.) h, significantly shorter (P < 0.005) than the mean value in non-smokers (12.0 +/- 3.1 h). These results suggest that cigarette smoking enhances the elimination of quinine. The clinical significance of these findings is unknown but they indicate the need for caution in the administration of quinine to patients who are heavy cigarette smokers.

Heat stroke-induced multiple organ failure.

The effect of excessive heat accumulated in the body is life threatening. It could damage not only body fluid electrolyte haemostasis, but kidney, liver, and hematologic function. The example reported herein was a Thai laborer, previously healthy, 32 years of age. He joined the tricycle race from Chiang Mai to Lumpoon, which is about 30 km. The tournament was held on a late morning of high humidity and a temperature of 35 degrees C. After biking 25 km, he began having heavy perspiration and suffered from severe myalgia and high fever. He suddenly lapsed into unconsciousness and fell down. He was admitted to the Lumpoon Hospital because of convulsions, and 2 days afterward, anuria, anemia, thrombocytopenia, coagulopathy, and liver impairment were detected. He was later transferred to the Faculty of Medicine for further intensive treatment. Lab analyses showed marked azotemia (BUN 96 mg%, Cr 10.6 mg%), elevation of muscle enzyme (CPK greater than 1000 U/L, SGOT greater than 650 U/L), liver failure (SGPT greater than 650 U/L, DB/TB = 23.0/30.0 mg%) and disseminated coagulopathy; platelet 17,000/mm3, PT 51.1 sec (control 12.5), and PTT 73.5 sec (control 37.7). He was treated with bicarbonated hemodialysis trice weekly. Blood-exchange transfusion was performed 3 times during the first 2 weeks with 10 units of fresh whole blood in each exchange. His ventilation required support by a ventilator. After a month, his consciousness, the liver function, and hematologic conditions became to recuperate. By 6 weeks postadmission, renal function eventually improved. This report is intended to warn the unprepared athlete entering an extreme, long-lasting exercise in an inappropriate climate.