Drug metabolism in diabetic subjects with fatty livers.

The effect of fatty degeneration of liver parenchyma on drug metabolism was investigated in 21 obese non-insulin-dependent diabetic subjects by measuring plasma antipyrine kinetics, hepatic cytochrome P-450, liver size and the extent of fatty infiltration. The hepatic drug metabolising capacity, as measured by total antipyrine clearance and the estimated total amount of cytochrome P-450, was at the same level as in non-diabetic control subjects with normal livers. Relative antipyrine clearance (per unit weight of liver) and cytochrome P-450 concentrations were significantly lower in the diabetics than in controls. The extent of fatty infiltration correlated poorly with the indices of drug metabolism. In non-insulin-dependent diabetics, slight to moderate hepatic fatty infiltration, without more serious structural distortion interfering with hepatic blood flow or hepatocellular function, seems to have only a minor influence on drug metabolism.

Hepatic blood flow and drug metabolism in patients on enzyme-inducing anticonvulsants.

Liver blood flow and indices of hepatic drug metabolism (antipyrine elimination rate and cytochrome P-450 concentration in liver biopsy specimens) were studied in 19 epileptics on long-term anticonvulsant treatment, and in 18 controls. The size of the liver and the total estimated liver blood flow were greater inthe epileptics than in the controls, whereas the relative liver blood flow (per unit weight of the liver) was not significantly different. The epileptics had higher cytochrome P-450 levels and they eliminated antipyrine faster than the controls. It was concluded that long-term ingestion of enzyme-inducing anticonvulsants is associated with an increase in the total hepatic blood flow in parallel with the increase in liver size, and not as an independent phenomenon. Since the relative perfusion rate of the hepatocytes was unchanged, the enhanced activity of drug metabolizing enzymes is presumed to be mainly responsible for the increased drug clearance observed in epileptic subjects.

Roles of hepatic blood flow and enzyme activity in the kinetics of propranolol and sotalol.

1 The roles of the hepatic blood flow and the drug oxidizing enzyme system in eliminating oral propranolol and sotalol were studied in twelve subjects with biopsy proven liver parenchymal disease. 2 The apparent plasma clearance of propranolol was closely related both to the in vivo (antipyrine test) and in vitro (cytochrome P-450) indices of the activity of the hepatic mixed function oxidase system. 3 Propranolol clearance had also a clear relationship to the estimated liver blood flow. Altered flow was, however, suggested to be a minor factor when compared with changes in the enzyme system. 4 The elimination rate of sotalol had no correlation to the indices of hepatic drug metabolism or to the estimated liver blood flow. 5 It is concluded that both the deteriorated sinusoidal perfusion and the decreased mass of drug metabolizing enzymes may be responsible for the impaired elimination of oral propranolol in subjects with parenchymal liver disease.

Comparison of three methods of measuring liver blood flow.

Liver blood flow was measured by dynamic 99Tcm-sulfur colloid accumulation and indocyanine green disappearance in 5 subjects, and by 99Tcm-sulfur colloid accumulation and 133Xe-wash-out in 7 subjects. Results obtained by the 99Tcm-sulfur colloid and indocyanine green methods were closely comparable, whereas the flow values estimated by the two isotope methods did not correlate well.

Methods for measuring the modulation transfer function of gamma camera systems.

The MTFs of three different gamma camera systems have been measured using two methods. In one method a step function was used as the object and the calculations were made by means of a pocket calculator. This method has been compared with a conventional line source method, where a computer is needed in performing the calculations. The methods give the same results with a fairly good accuracy. Both of the methods are well suited to a regular control of the condition and functioning of a gamma camera, provided that the camera is connected to a data-processing system so that the profile curves measured can be converted into the digital form.

Liver size and indices of drug metabolism in epileptics.

1 The relationship between liver size and in vivo (antipyrine kinetics) and in vitro (cytochrome P-450) drug metabolism was investigated in twenty-one epileptics on long-term anticonvulsant therapy and in controls. 2 The epileptics exhibited significant enlargement of the liver and enhancement of drug metabolism compared to the controls. 3 Liver size correlated to antipyrine kinetics only in controls. Concentration of cytochrome P-450 in liver biopsy specimens correlated with liver size neither in controls nor in epileptics. 4 The total hepatic cytochrome P-450, estimated on the basis of liver weight and cytochrome P-450 concentration of biopsy samples, correlated linearly with antipyrine kinetics, except in patients with the most severely disturbed liver architecture. 5 Measurement of liver size is essential when comparing in vivo and in vitro drug metabolism, but the changes in liver histology are also of great importance.

Liver size and indices of drug metabolism in alcoholics.

The role of liver size in drug metabolism was investigated in 34 chronic alcoholics and 28 controls by comparing antipyrine half-life with biopsy content and total amount of hepatic cytochrome P-450 (P-450) and liver weight. Liver size was significantly greater in alcoholics than in controls. Total P-450 was increased and antipyrine metabolism was enhanced in alcoholics with normal histology of the liver. In subjects with alcoholic hepatitis or cirrhosis, the antipyrine half-life was prolonged and P-450 was decreased. Alcoholics with fatty liver had a reduced P-450 content, but the total amount of P-450 and the antipyrine half-life were normal. The results demonstrate in alcoholics that an enlarged liver of normal histological appearance is associated with enhanced drug metabolism. In subjects with fatty liver the drug metabolizing capacity per unit weight of liver is often impaired, but the increase in liver size leads to undisturbed total oxidizing capacity and normal in vivo metabolism. In alcoholic hepatitis drug metabolism is impaired in spite of hepatomegaly. In cirrhosis the enlargement of the liver appears to compensate for the decreased P-450 content resulting in only slightly decreased total P-450, and the severly impaired in vivo drug metabolism may be due to derangement of blood flow.

Size and blood flow of the liver estimated by 99Tcm scanning.

In 14 healthy volunteers a method has been evaluated for simultaneous estimation of liver size and blood flow by dynamic gamma camera recording of Tc-sulfur colloid uptake in R--E cells of the liver. The reproducibility and convenience of the method was found to be such as to make it suitable for both scientific and routine clinical work.