Butylbiguanide concentration in plasma,liver, and intestine after intravenous and oral administration to man

Summary 50 mg¹⁴C-Butylbiguanide was administered intravenously to 4 diabetic patients and 100 mg¹⁴C-butylbiguanide orally to 5 further diabetics. The concentrations of the drug in plasma, intestinal fluid, intestinal epithelium and liver tissue were determined and the renal excretion of the biguanide measured. Irregularities in the plasma concentration curve were observed which appeared as systematic deviations from the ideal curve of a biexponential function. Because these deviations occurred only in the middle phase of the plasma concentration curve, it was nevertheless possible to calculate the pharmacokinetic parameters of butylbiguanide by use of a two-compartment open model. The principal pharmacokinetic parameters were determined according to this model after intravenous dosing and the following mean values were obtained:t _{1/2 ()}=4.6 h (=0.15 h^–1),C _P ⁰ =0.85µg/ml,V _D =218 l,V _T =157 l,V _P =62 l,k ₁₂=0.69 h^–1,k ₂₁=0.44 h^–1,k _el =0.54 h^–1. Within 48 h after administration, an average of 72.4% of the intravenous and 74.4% of the oral dose had been excreted in the urine. Total clearance (Cl _tot) averaged 536 ml/min and renal clearance (Cl _ren) 393 ml/min. High concentrations of butylbiguanide were observed in the intestinal fluid (100–700 mg/ml) 20–40 min after oral administration. It was found that the drug accumulates in intestinal fluid, intestinal epithelium and liver tissue, and that it is secreted into the intestinal lumen. The concentrations of butylbiguanide in intestinal and liver tissue were 10–46 times higher than in plasma. The secretion of biguanide into the intestinal lumen may occur via the bile or the intestinal mucosa, but there is no evidence of significant biliary excretion of butylbiguanide.