Disposition of Guanadrel in Subjects with Normal and Impaired Renal Function

Abstract

The disposition of a single 25 mg oral dose of guanadrel was evaluated in 22 subjects with various degrees of renal function. The terminal elimination half‐life was significantly prolonged in subjects with a creatinine clearance (Cl_Cr) < 30 mL/min/1.73 m² (19.2 ± 16.8 h) compared to 3.7 ± 1.9 h in subjects with a Cl_Cr > 80 mL/min/1.73 m.² Apparent total body clearance (Clp/F) was also progressively lower in the patients with decreased renal function and the decline was significantly correlated with Cl_Cr (Clp/F = 0.0294 + 0.0236 Cl_Cr, r = 0.74, P = 0.002). Renal clearance and apparent nonrenal clearance also declined as creatinine clearance decreased and both were significantly correlated with the observed Cl_Cr. Apparent volume of distribution averaged 11.5 ± 8.9 L/kg and did not differ in patients with decreased renal function compared to those with normal renal function. Thus, the disposition of guanadrel is significantly altered in the presence of renal insufficiency and dosage adjustments may be necessary, especially in patients with Cl_Cr < 50 ml/min.