RENAL CLEARANCE OF PYRIDOSTIGMINE IN MYASTHENIC PATIENTS AND VOLUNTEERS UNDER THE INFLUENCE OF RANITIDINE AND PIRENZEPINE

1. To assess the contribution of tubular secretion to the renal excret ion of pyridostigmine, and its modification by other cationic drugs, s ix volunteers were given single oral doses of 60-mg pyridostigmine bro mide with and without co-administration of ranitidine or pirenzepine. Renal clearances were determined by h.p.l.c. analysis of pyridostigmin e and enzymic measurement of endogenous creatinine in plasma and urine . 2. In patients with myasthenia receiving continuous pyridostigmine t herapy, renal clearance values were obtained in the same manner with a nd without ranitidine (10 patients) or pirenzepine (nine patients) co- medication. 3. Pyridostigmine was not bound to plasma proteins. Its re nal clearance averaged 6.65 ml/min per kg (350% of the creatinine clea rance) in all subjects, 74% being due to net tubular secretion. 4. Mea n values for pyridostigmine renal clearance and for clearance by secre tion were decreased in the presence of pirenzepine, but plasma concent rations were not affected significantly. Ranitidine caused a small non -significant decrease of the pyridostigmine clearance in patients. 5. Pyridostigmine had a higher elimination (2 h-1) than the absorption ra te constant (0.23 h-1) when administered orally as a non-retarded prep aration. 6. The renal clearance of creatinine was slightly increased b y pyridostigmine in volunteers and slightly decreased by pirenzepine i n the total group of subjects.