Clearances Of 51Cr-EDTA Research Articles

Effects of the xanthine oxidase inhibitor allopurinol on the renal clearance of nitroimidazoles

We have investigated the effects of the xanthine oxidase inhibitor allopurinol on the pharmacokinetics of nitroimidazoles in mice and dogs. Studies in mice showed that at a dose of 32 mg/kg given 30–60 min before, allopurinol had little or no effect on the clearance of misonidazole (MISO) or of the more lipophilic analogue Ro 07-0913, but did increase the blood concentrations of the hydrophilic dealkylation product desmethylmisonidazole (DEMIS). In addition, the clearances of administered DEMIS and the even more hydrophilic analogue SR-2508 were markedly reduced. This dose of allopurinol also caused a considerable fall in the clearances of 51Cr-EDTA and 125I-iodohippurate, normally used to measure glomerular filtration rate and effective renal plasma flow respectively. These data are consistent with a model in which allopurinol inhibits the renal clearance of hydrophilic nitroimidazoles. This leads to an increase in the acute toxicity of DEMIS and, to a lesser extent, of MISO. However, lower doses of allopurinol did not change the pharmacokinetics of MISO or DEMIS. A five-day pretreatment regimen (32 mg/kg/day) followed by a 66–76 hr recovery period was also without effect, thus demonstrating that the inhibition was reversible. Investigations in the dog showed that oral doses of 10–20 mg/kg allopurinol caused no change in the clearance of either 51Cr-EDTA or DEMIS.

Effect of cimetidine on renal function in man.

1 Renal function was studied in nine patients with chronic peptic ulcer before and at repeated intervals during treatment with cimetidine (1.6g daily). 2 Plasma creatinine concentration was significantly increased on the first day after starting cimetidine, and at 3 weeks, but not at 12 weeks. Blood urea concentration was unchanged. 3. Clearances of creatinine 51Cr EDTA and 125I-hippuran were significantly reduced within 6 h of starting cimetidine. Clearances of 51Cr EDTA and 125I-hippuran returned to baseline within 3 weeks, and creatinine clearance within 12 weeks. 4 Urinary creatine excretion was significantly increased at 3 weeks, but there was no significant change in urinary creatinine excretion, or in serum creatine phosphokinase concentration. 5. These observations suggest that cimetidine causes an early but short-lived fall in glomerular filtration rate (GFR) and effective renal plasma flow. The later rise in plasma creatinine was unaccompanied by any change in GFR, and may have been due to competition by cimetidine for renal tubular handling. 6 Caution should be exercised when administering cimetidine to patients with pre-existing renal failure.

Skeletal muscle oxygen pressure fields in artificially ventilated, critically ill patients.

The MDO (Mehrdraht Dortmund oberfläche) oxygen electrode was used in a study of skeletal muscle oxygen pressure fields, presented as histograms, in critically ill patients artificially ventilated with gas mixtures of different oxygen concentrations. The histograms were compared with forearm blood flow measurements performed with strain gauge plethysmography. Local blood flow and permeability-surface area product (PS) were also studied by the simultaneous clearances of 133xenon and 51Cr-EDTA. The histogram distribution type was normal, i.e. approximately Gaussian, at arterial oxygen pressure levels between 10 and 18 kPa. At arterial oxygen pressures outside this range the histogram distribution types were abnormal, i.e. they showed a non-symmetrical distribution of oxygen pressure values, but their mean was approximately the same as in the normal histogram. However, there were significantly higher tissue oxygen pressure mean values in the patients (3.43 kPa) than in a group of healthy human volunteers (2.25 kPa). Mean forearm blood flow and the clearances of 133xenon and 51Cr-EDTA showed marked variations during the measurements both intraindividually and interindividually. Mean forearm blood flow and mean clearances of 133xenon showed opposite trends compared with arterial oxygen pressures. Mean clearances of 51Cr--EDTA and means PS showed only minor variations at the different arterial oxygen pressure levels.

Skeletal muscle oxygen pressure fields in healthy human volunteers. A study of the normal state and the effects of different arterial oxygen pressures.

The MDO (Mehrdraht Dortmund Oberfläche)oxygen electrode was used for studies of tissue oxygen pressure fields (presented as histograms) in healthy human volunteers breathing room air and gas mixtures with different oxygen concentrations. Forearm blood flow measurements were performed with strain gauge plethysmography, and local blood flow and permeability-surface area product (PS) were studied by the clearances of 133xenon and 51Cr-EDTA. At ordinary arterial oxygen pressure levels the histograms were normal, i.e. their distribution type was approximately Gaussian. Higher arterial oxygen pressures caused changes in tissue oxygenation. However, at arterial oxygen pressure levels above 31 kPa two types of abnormal histogram distribution types were distinguished: scattered multi-population histograms (type a) and a type with predominantly low values (type b). Mean forearm blood flow showed only minor variations, whereas the clearances of 133xenon and 51Cr-EDTA were higher with higher PaO2. A parallel increase was also seen in PS.