The pharmacokinetic disposition of 5-fluorocytosine (5-FC) was studied in 7 patients with acute renal failure undergoing continuous hemofiltration (CH). CH was performed with a high-flux membrane and the average filtration rate (FR) was 16.3 ml/min. Following an intravenous loading dose of 2,500 mg, 5-FC concentrations were measured in plasma and ultrafiltrate. The half-lives of 5-FC were markedly prolonged in all patients, ranging from 15.9 to 37.2 h and longer half-lives corresponded to lower FR. The clearance of 5-FC averaged 97.5% of the FR. Within 48 h, 29–35% of the administered dose was recovered in the ultrafiltrate of 3 patients. The volume of distribution ranged from 0.772 to 0.982 l/kg. We found a linear relationship between the elimination rate constant and the FR, and based on these data, a dosage schedule is proposed regarding the use of 5-FC in patients treated with CH.

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SummaryIn a randomised, crossover trial the pharmacokinetics offurosemide (frusemide) were studied after single intravenous (3D-minute infusion of 120mg) and oral (500mg) doses in IO patients with chronic renal insufficiency (CLcR 16.7 ± 5.5 ml/min). Blood and urine samples were collected over 36 hours. Furosemide was analysed in serum and urine by a specific and sensitive HPLC method. After a lag time of 0.5 ± 0.5 hours (mean ± SD), peak plasma levels of 20.5 ± 12.0 mg/L were reached within 2.1 ± 0.7 hours. The mean plasma t'h of furosemide was 4.6 hours following intravenous administration and 11.8 hours after oral dosing (p = 0.0073). Within 24 hours, 14.9 ± 7.6% (IV) and 9.4 ± 5.5% (oral) of unchanged furosemide was excreted in the urine. The total body clearance was 46.3 ± 14.0 ml/min and the renal clearances amounted to 6.8 ± 3.9 (IV) and 5.5 ± 2.9 (oral) ml/min. The volume of distribution averaged 0.21 ± 0.07 L/kg. The absolute bioavailability of furosemide (67.9 ± 25.3%) was not affected by the chronic renal disease since it was comparable with data found in healthy subjects.

1. Roxatidine acetate, a new histamine H2‐receptor antagonist, was administered in the evening (75 mg p.o.) to eight patients with renal insufficiency (CLCR 8‐17 ml min‐1) for 12 days and plasma drug concentrations were measured. 2. Ambulatory intragastric pH was monitored following the last dose and values were compared with those on day 1 when all patients received a placebo. 3. The terminal elimination half‐life (mean +/‐ s.d.) of roxatidine was 10.8 +/‐ 2.4 h and its oral clearance was 178 +/‐ 43 ml min‐1. 4. During roxatidine treatment gastrin levels increased slightly (median 189 vs 289 ng l‐1) and the hyperparathyroid status of the patients was almost normalized (parathyroid hormone levels: median 199 vs 132 ng l‐1). 5. The mean latency to a gastric pH of at least 4 was 4.3 +/‐ 1.4 h. The duration of action (intragastric pH > 4) was 10.6 +/‐ 3.9 h. 6. As in a pilot study with six patients (CLCR < or = 17 ml min‐1) the recommended dosage regimen (75 mg 48 h‐1) was unable to maintain gastric pH > 4 for more than 6 h, daily nocturnal intake of 75 mg roxatidine acetate appears appropriate to elevate gastric pH > 4 for a sufficient period of time.