The oldest Eurasian hominoid.

Engelswies is an early Miocene vertebrate locality in southern Germany with a rich assemblage of terrestrial mammals, invertebrates and fossil plants. It is dated to 16.5-17.0 Ma based on magnetostratigraphy, biostratigraphy and lithostratigraphy, and includes among the faunal remains a hominoid upper molar fragment, the oldest hominoid so far identified from Europe. The evidence from Engelswies suggests that hominoids arrived in Eurasia about 17 Ma, roughly contemporaneously with pliopithecoids and Deinotherium, and before the last marine transgression to isolate Eurasia from Africa. Thick enamel and low dentine penetrance may have been key adaptations that contributed to the success of hominoids of dentally modern aspect in western Eurasia and ultimately to their ability to spread to eastern Eurasia and Africa in the middle and late Miocene.

High haemodialysis clearance of ornidazole in the presence of a negligible renal clearance.

The pharmacokinetics of ornidazole was studied in 6 patients treated by haemodialysis and in 8 subjects with a creatinine clearance between 4 and 99 ml/min x 1.73 m2. Blood and urine collections were performed for 72 h after i.v. and oral administration of 1.0 g ornidazole. Total body clearance, half-life, volume of distribution and systemic availability were independent of renal function and did not differ from previously reported values in normal volunteers. The haemodialysis clearance of ornidazole was greater than 100% higher than the total body clearance. The renal clearance of ornidazole accounted for less than 7% of the total body clearance. The percentage of the dose of ornidazole recovered in urine as parent compound or as the biologically active metabolites [alpha-(chloromethyl)-2 hydroxymethyl-5 nitroimidazole-1 ethanol and 3-(2 methyl-5 nitroimidazole-1-yl)1,2 propanediol] decreased linearly with decreasing renal function. Although the sum of those three compounds recovered in urine accounted for less than 10% of the total dose of ornidazole administered, they yielded therapeutic concentrations (greater than 4 micrograms/ml) in urine over 24 h after dosing. Due to the peculiar pharmacokinetic behaviour of ornidazole, i.e. high haemodialysis clearance in the absence of significant renal clearance, no dosage adjustment is necessary while renal function declines, but an increased dose is mandatory while patients are on dialysis.