, WI *This article represents the scientific opinion of many experts and, in particular, is derived from a series of workshops held under the auspices of the Federation International Pharmaceutique (FIP) and cosponsored by the Royal Pharmaceutical Society (UK), the Bundesverband der Pharmazeutischen Industrie (BPI), Colloquium Pharmaceuticum (Germany), the American Association of Pharmaceutical Scientists (AAPS, US), and the US Food and Drug Administration. It is

Nifedipine kinetics have not been described in clinically relevant detail because of difficulties in formulating a stable preparation for intravenous use and lack of a specific and sensitive assay for plasma nifedipine. We recently developed a gas-chromatographic method and determined conditions in which nifedipine could be protected from photodegradation. Therefore, we evaluated the kinetics and bioavailability of nifedipine in 12 normal subjects after single intravenous (1 mg/5 min) and oral (10 mg) doses. After intravenous dosing, the drug was eliminated with a half-time of 1.77 +/- 0.25 hour, and total clearance was calculated at 0.62 +/- 0.09 liter/kg/hr. With oral drug administration, the elimination half-time was twice as long for the group; but within these subjects, marked variability in the rate of appearance of the drug in plasma was observed, giving profiles consistent with fast and slow absorption. In the latter group, peak plasma drug concentrations were only one third the level seen in those exhibiting a faster absorption profile, although the extent of drug absorption (as derived from areas under the plasma level-time curves) did not vary. Bioavailability was 0.45 +/- 0.08. Untoward effects resulting from the drug's pharmaco-subjects after intravenous administration (flushing).

Non-technical summaryA poor diet during pregnancy has been linked to long-term health outcomes for the baby, such as an increased risk of diseases of the heart and kidney. We show in an experimental model that recreates a poor diet during pregnancy, i.e. a diet low in protein with adequate energy, that kidney development in the baby is affected in such a way as to reduce the potential for new blood vessels to form. This results in a greater number of important, functional kidney cells spontaneously dying. Later in life, these effects in the kidney manifest as permanently reduced kidney function, especially if the baby subsequently becomes overweight as an adult. The research reinforces advice to pregnant mothers about the importance of eating a nutritionally balanced diet during pregnancy.AbstractA nutritionally poor maternal diet can reduce nephron endowment and pre-empt premature expression of markers for chronic renal disease in the offspring. A mechanistic pathway from variation in maternal diet through altered fetal renal development to compromised adult kidney structure and function with adult-onset obesity has not been described. We show that maternal protein-energy malnutrition in sheep blunts nephrogenic potential in the 0.44 gestation (65 days gestation, term ∼147 days) fetus by increasing apoptosis and decreasing angiogenesis in the nephrogenic zone, effects that were more marked in male fetuses. As adults, the low-protein-exposed sheep had reduced glomerular number and microvascular rarefaction in their kidneys compensated for, respectively, by glomerular hypertrophy and increased angiogenic support. In this study, the long-term mild anatomical deficits in the kidney would have remained asymptomatic in the lean state, but when superimposed on the broad metabolic challenge that obesity represents then microalbuminuria and blunted bilateral renal function revealed a long-term physiological compromise, that is only predicted to worsen with age. In conclusion, maternal protein-energy malnutrition specifically impacts fetal kidney vascular development and prevents full functionality of the adult kidney being achieved; these residual deficits are predicted to significantly increase the expected incidence of chronic kidney disease in prenatally undernourished individuals especially when coupled with a Western obesogenic environment.

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