Effects of liver disease on the disposition of ciramadol in humans.

To determine the effects of liver disease on the disposition of ciramadol, an analgesic that undergoes ether glucuronidation, we studied its plasma pharmacokinetics in 10 patients with stable cirrhosis, 8 with acute viral hepatitis, and 16 age-matched healthy controls. Renal excretion of the glucuronides was also determined. In healthy controls given a single intravenous dose of the drug the t 1/2 was 3.4 +/- 0.3 hrs and the systemic clearance was 668 +/- 109 ml/min of which renal clearance was 320 +/- 73 ml/min and non-renal clearance 349 +/- 74 ml/min. The corresponding values after an oral dose were similar. Renal clearance was related directly to the estimated creatinine clearance. Moreover, the renal clearance of ciramadol exceeded creatinine clearance, suggesting that the drug was excreted not only by glomerular filtration but also by tubular secretion. The systemic clearance of intravenous ciramadol was diminished by 40% in cirrhosis, P less than 0.05, due to a reduction in renal clearance, while non-renal clearance remained normal. Renal clearance of the inactive glucuronides, on the other hand, was not affected. In patients with acute viral hepatitis, systemic clearance was unchanged, but renal clearance of ciramadol tended to increase during the acute phase of the disease and to return toward normal after recovery. Renal excretion of the inactive glucuronides was decreased by 48% (P less than .05). These findings suggest that the non-renal ether glucuronidation of ciramadol remains intact in patients with stable cirrhosis or acute viral hepatitis. However, the renal clearance of the drug may be impaired in cirrhosis, but tends to be enhanced in acute hepatitis.(ABSTRACT TRUNCATED AT 250 WORDS)

Stabilization procedures in the patient with acute spinal cord injury.

In summary, when confronted with the spinal-cord-injured patient, the surgeon must do an initial evaluation with a complete history and physical examination, order the appropriate radiographic studies, determine the stability of the spinal column, and initiate treatment with stabilization techniques. An overview of surgical stabilization procedures used for the treatment of acute spinal cord injuries has been presented. The concept of spinal stability and the determination of the location of spinal cord compression are used to determine which surgical technique should be used. With appropriate decompression and/or stabilization procedures or both, spinal-cord-injured patients may regain additional function and begin an early rehabilitation program.

Lack of effect of nizatidine on hepatic drug metabolism in man.

The effect of nizatidine, a new H2-receptor antagonist, on the hepatic metabolism of three probe drugs was studied in normal volunteers. The drugs studied were chlordiazepoxide and theophylline which are metabolized in part by N-demethylation by the hepatic microsomal cytochrome P-450 system and lorazepam which is conjugated to lorazepam glucuronide. A 7 day course of nizatidine did not interfere with the disposition of any of these therapeutic agents in man.