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PubMed1987

Pharmacokinetics of leucovorin (D,L-5-formyltetrahydrofolate) after intravenous injection and constant intravenous infusion.

The pharmacokinetics of the active and inactive diastereoisomers of leucovorin and its active metabolite, 5-methyltetrahydrofolate (5-CH3-THF) were studied after iv injection of leucovorin in normal human subjects at a dose of 28 mg/m2, and in patients given 500 mg/m2 daily by constant iv infusion for a 5.5 day period. In both studies the plasma half-life (t1/2) of the active isomer, L-formyltetrahydrofolate (CHO-THF), was only 32 to 35 minutes, whereas the inactive isomer, D-CHO-THF had a plasma t 1/2 of 352 to 485 minutes. During constant infusion, the plasma levels reached plateaus of 2.33 and 37.5 microM for L-CHO-THF and D-CHO-THF, respectively. The inactive isomer was cleared from plasma only by urinary excretion of the unchanged drug. The active isomer was also excreted unchanged in the urine but in addition was extensively metabolized to the active metabolite L-5-CH3-THF. The active metabolite achieved a plasma level of 4.85 microM during constant infusion and appeared to have a longer t 1/2 after constant infusion than was observed after iv injection. Furthermore a larger apparent volume of distribution (Vd) of 5-CH3-THF was obtained in the constant infusion study. These findings suggest that constant iv infusion of large doses of leucovorin can considerably expand the intracellular pools of active folate. The consequence of the extensive accumulation of the inactive isomer, D-CHO-THF, is not known. However, the small Vd of D-CHO-THF suggests that it does not extensively accumulate in tissues.

Biotransformation↗
PubMed1995

Comparative disposition of morphine-3-glucuronide during separate intravenous infusions of morphine and morphine-3-glucuronide in sheep. Importance of the kidney.

The disposition of morphine-3-glucuronide (M3G) in sheep was compared during separate constant infusions of morphine and M3G. Five ewes received a 15-min loading dose, followed by a constant infusion of morphine sulfate (10 mg/hr) or M3G (4 mg/hr for 4 sheep, 7.5 mg/hr for 1 sheep) for a further 5.75 hr. During the 5th-6th hr of infusion, blood was collected simultaneously from the aorta, pulmonary artery, hepatic vein, hepatic portal vein, renal vein, and posterior vena cava. Additional samples were collected from the aorta from 0 to 5 hr and from 6 to 48 hr. Urine was collected via an indwelling catheter from 0 to 6 hr, with further free-flowing urine up to 48 hr. An HPLC assay was used to determine simultaneously morphine, M3G, and morphine-6-glucuronide (M6G) in plasma and urine. Constant concentrations of morphine, M3G, and M6G in plasma were achieved during the 5- to 6-hr period of infusion with morphine, as were the concentrations of M3G while M3G was infused. Regional net extraction ratios and total and regional clearances were calculated during the 5- to 6-hr period. After the infusions were ceased, there was prolonged elimination of M3G formed in situ from morphine compared to when infused as M3G. No morphine or M6G was detected in the plasma during and after infusion with M3G, nor were they found in urine collected up to 6 hr.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

The effect of L-carnitine, administered through intravenous infusion of glucose, on both glucose and insulin levels in healthy subjects.

The goal of the present study was to evaluate the effect of L-carnitine on plasma glucose and insulin levels. Two parallel studies were set-up, of 40 and 20 healthy volunteers, respectively. Each group received 500 cc of 10% glucose or 5% glucose, to which were randomly added 4 g or 2 g of L-carnitine and administered a week apart. Results showed that L-carnitine was able to reduce the increase in glucose plasma levels induced by infusion of the glucose solution. This finding was not dependent on an insulin-dependent mechanism.

Adult↗