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C Y Lui

Publications and source records attributed to C Y Lui.

27 records · Page 2Linked to original sources
PubMed1985

Urinary pH and urine flow independent renal clearance of methotrexate in dogs.

The effects of urine flow and pH on methotrexate renal clearance were studied in seven conditioned male Beagle-Mongrel dogs. Steady-state plasma methotrexate and inulin concentrations were achieved by i.v. infusions preceded by i.v. bolus doses. Plasma and urine concentrations of methotrexate were quantitated by a sensitive high-performance liquid chromatographic assay, while those of inulin were measured by a colorimetric method. Since plasma protein binding of methotrexate was pH and concentration independent, methotrexate/inulin renal clearance without correcting for plasma binding was used for most of the data analyses. The results showed that the renal clearance ratios at the plasma methotrexate levels (approximately 0.1, 1.0, 20.0 and 100 micrograms/ml) studied remained relatively constant when urine pH (differences of up to about 2.5 units) and flow rate (differences of up to approximately 30 times) were changed. This indicated that renal reabsorption of methotrexate in these dogs was negligible. However, concentration-dependent renal clearance was observed. The mean renal clearances were 3.84, 3.94, 2.73, and 2.72 ml/min/kg at plasma concentrations of about 0.1, 1.0, 20.0, and 100.0 micrograms/ml, respectively, when urine was alkalized by sodium bicarbonate. The corresponding clearances were 4.02, 4.28, 2.62,and 2.65 ml/min/kg when urine was acidified by ammonium chloride. These showed the existence of saturable tubular secretion of methotrexate. No 7-hydroxy-methotrexate, a metabolite found in other species, was detected in the urine and plasma of the dogs.

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PubMed1985

Clearance studies of methotrexate in dogs after multiple-rate infusion.

Plasma, renal, and nonrenal clearances of methotrexate as well as their interrelationship were studied in five conditioned male beagle-mongrel dogs using the multiple-rate infusion method. Steady-state plasma methotrexate concentrations of 1, 20, and 100 micrograms/ml were targeted for by i.v. bolus doses followed by i.v. infusions. An isotonic solution of sodium bicarbonate or ammonium chloride was simultaneously infused to study the effect of acid-base imbalance on the clearances. NaCl solution (0.9%) infusion served as a control. Plasma and urine concentrations of methotrexate were quantitated by a sensitive high-performance liquid chromatographic method. Distortion of body acid-base balance did not significantly change the clearances of methotrexate. The results showed that the plasma clearance (4.02 to 4.68 ml/min/kg) of methotrexate was relatively constant over the concentration range studied. The renal and nonrenal clearances, on the other hand, were concentration dependent. As the plasma methotrexate concentration increased from 1 to 20 or 100 micrograms/ml, renal clearance decreased from 3.60 to 4.28 ml/min/kg to 2.62 to 2.73 ml/min/kg, and nonrenal clearance increased form 0.35 to 0.42 ml/min/kg to 1.38 to 1.74 ml/min/kg. Concentration-dependent renal clearance may be due to saturation of the process involving active tubular secretion of methotrexate.

Animals↗
PubMed1984

Concentration and pH dependent steady-state volume of distribution of methotrexate estimated by a simple physiologically based method.

The effects of plasma concentration and pH on the steady-state volume of distribution, Vss, of methotrexate (MTX) were studied in five conditioned male beagle-mongrel dogs. Steady-state plasma MTX concentrations of approximately 1, 20, and 100 micrograms/ml were targeted for by i.v. bolus doses followed by i.v. infusions. An isotonic solution of sodium bicarbonate or ammonium chloride was simultaneously infused for the purpose of inducing plasma pH change, while the infusion of an isotonic solution of sodium chloride served as a control. Plasma and urine concentrations of MTX were quantitated by a sensitive high-performance liquid chromatographic method, and the Vss of MTX was estimated by a recently reported physiologically based method of Chiou and Lam. Statistically significant (p less than 0.05) concentration and plasma pH dependent Vss of MTX were observed. Concentration dependence of Vss was noted in sodium chloride and ammonium chloride infused dogs, but not in bicarbonate treated dogs. There was an average 50.0 and 44.8% increase in Vss at 1 microgram/ml relative to the two higher concentrations (20 and 100 micrograms/ml) for dogs treated with ammonium and sodium chloride, respectively. However, Vss of MTX at the targeted concentrations of 20 and 100 micrograms/ml was relatively constant. Plasma pH dependence of Vss was observed only at the plasma concentration of 1 microgram/ml, and on the average, ammonium chloride and sodium chloride treatments resulted in 50.0 and 31.3% higher Vss, respectively, when compared with the bicarbonate treatment. These phenomena appear to be adequately explained by the reported tissue uptake kinetics of MTX.

Animals↗
PubMed1984

Pharmacokinetics in blood IV: unusual distribution, storage effect and metabolism of methotrexate.

The whole blood from three human subjects, one dog and four rabbits was spiked with methotrexate (MTX) to yield appropriate concentrations, and was incubated at 37 degrees C and 50 oscillations per min. MTX was found to exhibit unusual distribution kinetics in whole blood; plasma MTX concentrations generally dropped to a minimum at about 5 min then increased and fluctuated somewhat irregularly afterwards. Differences of up to 21, 19 and 32% between maximum and minimum were found in the studies from human, dog and rabbit, respectively. These unusual distribution phenomena might be due to the Schiff base formation between free primary amino group(s) of MTX and free fatty aldehyde groups on blood cell membrane. Similar unusual distribution kinetics were observed with blood from three human subjects after kept at room temperature or in the refrigerator, and blood collected from three dogs after intravenous bolus or infusion of MTX. Formation of three metabolites including 7-hydroxymethotrexate was only found in blood from rabbits, but not from humans and dogs.

Animals↗
PubMedDate not supplied

Renal and non-renal clearances of iothalamate.

An evaluation of the literature indicated that certain aspects of the disposition kinetics of iothalamate, important to the accurate determination of glomerular filtration rate in dogs and humans, remain to be resolved. The simultaneous clearances of iothalamate and inulin in 5 dogs were determined at three steady-state iothalamate plasma levels (2, 10, and 40 micrograms ml-1) following various rates of intravenous infusion. The iothalamate clearances, both renal and non-renal, were concentration-independent. The overall mean non-renal clearance was 18 per cent (ranging from 9 to 25 per cent) of its plasma clearance. The mean iothalamate/inulin renal clearance ratio was about 0.84 with individual values ranging from 0.72 to 0.95. The significant (4-26 per cent) plasma protein binding of iothalamate in these dogs was the main reason for the lower-than-unity clearance ratios obtained. The literature indicates the existence of up to 25 per cent of non-renal elimination in humans with normal renal function; this is comparable to the present results obtained with dogs but contrary to the assumption, sometimes reported in the literature that non-renal elimination is essentially absent in humans. Binding of iothalamate to plasma proteins from humans was not found in the present study. The above results suggest that for accurate glomerular filtration rate determination in humans and dogs, especially for those with renal impairment, renal clearance rather than plasma clearance should be used, and in the case of dogs it should also be corrected for plasma protein binding. Iothalamate in plasma and urine was analysed by a simple, micro high-performance liquid chromatographic method with UV detection.

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