Summary:Purpose: To study pharmacokinetics of levetiracetam (LEV) during pregnancy, delivery, lactation, and in the neonatal period.Methods: Fourteen women with epilepsy receiving LEV treatment during pregnancy and lactation contributed with 15 pregnancies to this prospective study in which LEV concentrations in plasma and breast milk were determined. Trough maternal plasma samples were collected each trimester, and at baseline after delivery. Blood samples were obtained at delivery from mothers, from the umbilical cord, and from newborns during 2 days after delivery. LEV concentration was also determined in breast milk and in plasma collected from 11 of the mothers and their suckling infants after birth.Results: The umbilical cord/maternal plasma concentration ratios ranged from 0.56-2.0 (mean 1.15, n = 13). LEV plasma concentrations in the neonates declined with an estimated halflife of 18 h (n = 13). The mean milk/maternal plasma concentration ratio was 1.05 (range, 0.78-1.55, n = 11). The infant dose of LEV was estimated to 2.4 mg/kg/day, equivalent to 7.9% of the weight-normalized maternal dose. Plasma concentrations in breastfed were approximately 13% of the mother's plasma levels. Maternal plasma concentrations during third trimester were only 40% of baseline concentrations outside pregnancy (p < 0.001, n = 7)Conclusions: Our observations suggest considerable transplacental transport of LEV and fairly slow elimination in the neonate. Plasma concentrations of LEV in nursed infants are low despite an extensive transfer of LEV into breast milk. Pregnancy appears to enhance the elimination of LEV resulting in marked decline in plasma concentration, which suggests that therapeutic monitoring may be of value.

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Carbonic anhydrase isozymes CA I and CA II were assayed by a radio-immunosorbent technique in the plasma and urine of apparently healthy subjects and of patients with renal disease. The concentrations (mean +/- SD, n = 8) of CA I and CA II in the plasma of healthy subjects were 2.3 +/- 2.3 and 0.8 +/- 0.5 mg/l, respectively. The urinary excretion values were 3.8 +/- 2.0 and 3.5 +/- 1.9 micrograms/24 h, and the apparent renal clearances were 21 +/- 17 and 52 +/- 44 microliters/min, respectively, values that are similar to those of other low molecular weight proteins. CA I and CA II have mol. wt of 28,850 and 29,300, respectively, they are globular in shape and have a Stoke-Einstein radius of 25 A. They could, therefore, be expected to be filtered at the glomeruli and thereafter reabsorbed by the proximal tubules. CA II is also present in the cytoplasm of renal proximal and distal tubular cells. A study of the pattern of urinary excretion of CA I and CA II could permit detection of damage to renal tubular cells in two ways--either from defective reabsorption of filtered CA I and CA II by the proximal tubular cells, or from leakage of CA II from the proximal or distal tubules into the urine. Some patients with hypercalcuria and renal tubular acidosis showed increased excretion of these enzyme proteins and of beta 2-microglobulin (BMG) into the urine, but the prevalence was rather low (27%). Further studies of patients with more severely damaged kidneys are required.

Twenty-three patients with severe hypertension and impaired renal function were included in an open study of the efficacy and tolerance of felodipine treatment over 6 months. All patients were previously treated with a diuretic, a beta blocker, and a vasodilator, and eight of them also received an ACE inhibitor. At the start of felodipine treatment the previously used vasodilator was withdrawn. In nine patients the concomitant antihypertensive treatment was reduced during the study. The glomerular filtration rate (GFR), as 51Cr EDTA clearance, was determined before and at the end of the study. The blood pressure (BP) and heart rate (HR) were recorded at all clinical visits in the morning 12 hours after the evening dose of felodipine and 2 hours after the morning dose. Plasma concentrations of felodipine were measured at every visit before the morning dose and 2 hours after dose. The BP was reduced after felodipine was substituted for the previously used vasodilator. A significant additional anti-hypertensive effect was recorded 2 hours after the dose and amounted to -37 +/- 22/-15 +/- 12 mmHg (p = 0.0001/p = 0.0002) at 6 months. The effect measured 12 hours after the dose was less pronounced and was -11 +/- 28/-6 +/- 10 mmHg (p = 0.15/p = 0.03). Mean GFR was unchanged during the study, 38 +/- 19 versus 38 +/- 19 ml/min (n = 16). There was a sixfold interindividual variation in the trough plasma concentrations at steady state at the same drug dosage. Higher plasma concentrations seemed to be required to achieve the same antihypertensive effects as in patients with less severe hypertension and normal renal function.(ABSTRACT TRUNCATED AT 250 WORDS)