Isoprene is a normal constituent of human breath and may be derived from the cholesterol synthetic pathway. Acute and chronic lovastatin and a cholesterol-supplemented diet were used to determine whether a mechanistic link exists between isoprene and cholesterol biosynthesis in vivo in humans. The acute effects of lovastatin, a competitive inhibitor of the rate-limiting step of cholesterol biosynthesis, on breath isoprene excretion was determined by administering a single 20, 40 or 80 mg dose of this drug to five healthy male subjects at 8 p.m. and measuring their breath isoprene levels every 4 h for one 24 h cycle before and after treatment. When compared to the baseline cycle, all three doses of lovastatin significantly reduced breath isoprene levels at 6 and 10 h post-drug treatment. Chronic lovastatin therapy (40 mg b.i.d. for 6 wk) reduced 6 a.m. breath isoprene levels (time of maximum baseline value) by 27 +/- 9% (SEM) and cholesterol synthesis measured in freshly isolated mononuclear leukocytes (ML) by 12 +/- 6%. A cholesterol-supplemented diet (1070 mg, total) ingested for 6 wk reduced breath isoprene excretion and ML sterol synthesis by 16 +/- 5 and 19 +/- 4%, respectively. The parallel decreases in isoprene excretion and cholesterol synthesis caused by these pharmacologic and dietary means suggest that breath isoprene is derived from the cholesterol synthesis pathway.

We tested the possibility that simvastatin, a competitive inhibitor of HMG-CoA reductase related to mevinolin, might alter cholesterol saturation of gallbladder bile. Ten patients with Type IIa or IIb hypercholesterolemia underwent bile sampling before, and again after, treatment with 20 or 40 mg per day simvastatin for 7 to 13 weeks. Mean cholesterol saturation index of gallbladder bile fell from 1.01 to 0.77 during simvastatin treatment (p less than 0.01). This finding strongly suggests that treatment with HMG-CoA reductase inhibitors will not predispose to development of cholesterol gallstones. Indeed, it raises the possibility that such inhibitors might have a future role to play in treatment of gallstones.

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A B S T R A C T Pure amylase was isolated from pancreata and parotid glands of the baboon, an animal which has a serum amylase level and renal clearance of amylase (CAm) similar to man. After bolus injection, both pancreatic and salivary amylase rapidly disappeared from the serum in a monoexponential fashion with a mean serum half-time of approximately 83 min. Only about 24% of the amylase cleared from the serum appeared in the urine indicating that the majority of amylase was removed from the serum by an extraurinary mechanism. The CA. by the kidney was constant over a wide range of serum amylase levels and the ratio of CAm/CI, which averaged 3.0%, was not influenced by mannitol diuresis. This suggests that the renal excretion of amylase results from glomerular filtration without appreciable tubular reabsorption. Pancreatic amylase was consistently cleared more rapidly by the kidney than was the baboon's endogenous amylase while salivary amylase was consistently cleared less rapidly than endogenous amylase.The findings in this study provide insight into several of the following clinically observed phenomena: (a) the short serum half-time of atpylase accounts for the transient nature of serum amylase elevations in pancreatitis; (b) the extra-urinary removal of amylase accounts for the maintenance of relatively normal amylase levels in uremia; and (c) the more rapid renal clearance of pancreatic amylase compared to salivary amylase may explain the disproportionate elevation of the urinary amylase excretion rate relative to the serum amylase level in acute pancreatitis.