AGING EFFECTS ON THE ORGANIC-BASE TRANSPORTER AND STEREOSELECTIVE RENAL CLEARANCE

Objective: The organic base transporter is responsible for stereoselec tive renal excretion. Changes in activity of this system secondary to aging may affect the disposition of an organic base in a stereoselecti ve manner. Methods: Eight young men (age range, 22 to 33 years) and se ven elderly men (age range, 62 to 79 years) were given 10 mg pindolol twice daily, pindolol with 200 mg trimethoprim once daily (a known inh ibitor of organic base secretion) and pindolol with 1.5 gm ammonium ch loride (NH4Cl) four times daily for 3 days on three occasions. On day 4, urine and plasma were collected over 24 hours to determine renal cl earance (CLR) values of pindolol isomers. Results: R(+)-Pindolol CLR v alues in young versus elderly men were 203 +/- 82 versus 150 +/- 87 ml /min, 128 +/- 51 versus 113 +/- 35 ml/min, and 480 +/- 248 versus 247 +/- 59 ml/min during the control, trimethoprim, and NH4Cl study phases , respectively. S(-)-Pindolol CL,values in young versus elderly were 2 79 +/- 81 versus 207 +/- 105 ml/min, 178 +/- 70 versus 136 +/- 42 ml/m in, and 593 +/- 294 versus 276 + 49 ml/min during control, trimethopri m, and NH4Cl phases, respectively. NH,CI increased R(+)-pindolol CLR b y 138% (p < 0.05 versus pindolol alone) in young men, which was signif icantly greater than that observed in elderly subjects (66%; p < 0.05 versus pindolol alone; p = 0.016 young versus old). NH4Cl affected S(- )-pindolol CLR in a similar manner. Trimethoprim decreased R(+)-pindol ol CLR in the young subjects by 37% (p < 0.05 versus pindolol alone), which was similar to that observed in the elderly subjects (26%; p < 0 .05 versus pindolol atone; p = 0.94 young versus elderly). Tritmethopr im affected S(-)-pindolol CLR in a similar manner. Stereoselective ren al excretion of pindolol mas unaffected by NH4Cl and trimethoprim, whe re the R(+)/S(-)-pindolol CLR ratio was unchanged (p = NS) from contro l in the young and elderly subjects. Comparison of the pindolol CLR is omer ratio between young and elderly groups showed no significant diff erences. Changes in pindolol clearance values resulted in significant changes in beta-blocking activity, assessed by isoproterenol (INN, iso prenaline) testing. Conclusions: Trimethoprim and NH4Cl significantly affect pindolol renal and total clearance values. Aging does not alter renal excretion of pindolol except for the magnitude by which renal e xcretion can be stimulated.