Safety Pharmacology of Drugs for the Urinary Tract
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I.E.1 I.E.1.1 I.E.1.1.1 I.E.1.1.2
I.E.1.1.3 I.E.1.1.4 I.E.1.1.5 I.E.1.1.6 I.E.1.1.7 I.E.1.1.8 I.E.1.2 I.E.1.2.1 I.E.1.2.2 I.E.1.2.3 I.E.1.2.4 I.E.1.2.5 I.E.1.2.6 I.E.1.2.7 I.E.1.2.8
I.E.1.2.9 I.E.1.2.10 I.E.2 I.E.2.1 I.E.2.2
General Functional Assessments . 96 In vitro and in situ Assessments . . . . 96 Carbonic Anhydrase Inhibition in vitro . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96 Inhibition of Xanthine Oxidase in vitro Indicating Hypouricemic Activity . . . . . . . . . . . . 97 Urate Uptake in Brush Border Membrane Vesicles . . . . . . . . . . . . . . . . 97 Patch Clamp Technique in Kidney Cells . . . . . . . . . . . . . . . . . . . . 98 Perfusion of Isolated Kidney Tubules . . . . . . . . . . . . . . . . . . . . . . . . . . . 99 Isolated Perfused Kidney . . . . . . . . 102 Micropuncture Techniques in the Rat . . . . . . . . . . . . . . . . . . . . . . . 103 Stop Flow Techniques . . . . . . . . . . . 104 In vivo Techniques . . . . . . . . . . . . . . 104 Diuretic Activity in Rats (LIPSCHITZ Test) . . . . . . . . . . . . . . 104 Saluretic Activity in Rats . . . . . . . . 105 Diuretic and Saluretic Activity in Dogs . . . . . . . . . . . . . . . . . . . . . . . . . 106 Evaluation of Renal Concentrating Ability . . . 107 Clearance Methods . . . . . . . . . . . . . . 108 Fractional Excretion Methods . . . . 110 Diuretic and Uricosuric Activity in Mice . . . . . . . . . . . . . . . . . . . . . . . . . 112 Inhibition of Allantoxanamide-Induced Hyperuricemia in Rats . . . . . . . . . . . 113 Phenol Red Excretion in Rats . . . . 113 Uricosuric Activity in Relevant Animal Models . . . . . . 114 Assessment of Renal Injury . . . . 115 Assessment of Renal Injury by Serum Chemistry . . . . . . . . . . . . . 115 Assessment of Renal Injury by Urinalysis . . . . . . . . . . . . . . . . . . . . 117
I.E.2.3 I.E.2.4 I.E.3 I.E.3.1 I.E.3.2
I.E.3.3 I.E.3.4 I.E.4 I.E.4.1 I.E.4.1.1 I.E.4.2 I.E.4.2.1 I.E.4.2.2 I.E.4.2.3 I.E.4.2.4
Assessment of Renal Injury by Urine Proteins . . . . . . . . . . . . . . . . Assessment of Renal Injury by Urine Enzymes . . . . . . . . . . . . . . . Experimental Models of Renal Failure . . . . . . . . . . . . . . . . Chronic Renal Failure in the Rat. . Chronic Renal Failure after Subtotal (Five-Sixths) Nephrectomy in Rats . . . . . . . . . . . . Experimental (Immune-Mediated) Glomerulonephritis . . . . . . . . . . . . . . Toxicant-Induced Renal Injury . . . Assessment of the Lower Urinary Tract . . . . . In vivo Studies . . . . . . . . . . . . . . . . . . Micturition Studies . . . . . . . . . . . . . . Studies in Isolated Organs . . . . . . . Studies on Renal Pelvis . . . . . . . . . . Studies on the Urinary Bladder and Internal Urethral Sphincter . . . Effects on the External Urethral Sphincter Propagation of Impulses in the Guinea Pig Ureter . . . . . . . . .
119 121 124 124
125 128 131 133 133 133 135 135 137 139 140
Based on the second edition of “Drug Discovery and Evaluation – Pharmacological Assays” edited by H.G. Vogel, Springer-Verlag 2002, with contributions by H.G. Vogel,
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