Semiphysiologically based pharmacokinetic model for midazolam and CYP3A mediated metabolite 1-OH-midazolam in morbidly obese and weight loss surgery patients

This study aimed to describe the pharmacokinetics of midazolam and its cytochrome P450 3A (CYP3A) mediated metabolite 1-OH-midazolam in morbidly obese patients receiving oral and i.v. midazolam before (n = 20) and one year after weight loss surgery (n = 18), thereby providing insight into the influence of weight loss surgery on CYP3A activity in the gut wall and liver. In a semiphysiologically based pharmacokinetic (semi-PBPK) model in which different blood flow scenarios were evaluated, intrinsic hepatic clearance of midazolam (CLint,H) was 2 (95% CI 1.40-1.64) times higher compared to morbidly obese patients before surgery (P  0.05), with low values for both groups. The results of the semi-PBPK model suggest that, in patients after weight loss surgery, CYP3A hepatic metabolizing capacity seems to recover compared to morbidly obese patients, whereas CYP3A mediated CLint,G was low for both populations and showed large interindividual variability.Pharmacolog

The extremal limits of the C-metric: Nariai, Bertotti-Robinson and anti-Nariai C-metrics

In two previous papers we have analyzed the C-metric in a background with a cosmological constant, namely the de Sitter (dS) C-metric, and the anti-de Sitter (AdS) C-metric, following the work of Kinnersley and Walker for the flat C-metric. These exact solutions describe a pair of accelerated black holes in the flat or cosmological constant background, with the acceleration A being provided by a strut in-between that pushes away the two black holes. In this paper we analyze the extremal limits of the C-metric in a background with generic cosmological constant. We follow a procedure first introduced by Ginsparg and Perry in which the Nariai solution, a spacetime which is the direct topological product of the 2-dimensional dS and a 2-sphere, is generated from the four-dimensional dS-Schwarzschild solution by taking an appropriate limit, where the black hole event horizon approaches the cosmological horizon. Similarly, one can generate the Bertotti-Robinson metric from the Reissner-Nordstrom metric by taking the limit of the Cauchy horizon going into the event horizon of the black hole, as well as the anti-Nariai by taking an appropriate solution and limit. Using these methods we generate the C-metric counterparts of the Nariai, Bertotti-Robinson and anti-Nariai solutions, among others. One expects that the solutions found in this paper are unstable and decay into a slightly non-extreme black hole pair accelerated by a strut or by strings. Moreover, the Euclidean version of these solutions mediate the quantum process of black hole pair creation, that accompanies the decay of the dS and AdS spaces

Neutrino Interferometry In Curved Spacetime

Gravitational lensing introduces the possibility of multiple (macroscopic) paths from an astrophysical neutrino source to a detector. Such a multiplicity of paths can allow for quantum mechanical interference to take place that is qualitatively different to neutrino oscillations in flat space. After an illustrative example clarifying some under-appreciated subtleties of the phase calculation, we derive the form of the quantum mechanical phase for a neutrino mass eigenstate propagating non-radially through a Schwarzschild metric. We subsequently determine the form of the interference pattern seen at a detector. We show that the neutrino signal from a supernova could exhibit the interference effects we discuss were it lensed by an object in a suitable mass range. We finally conclude, however, that -- given current neutrino detector technology -- the probability of such lensing occurring for a (neutrino-detectable) supernova is tiny in the immediate future.Comment: 25 pages, 1 .eps figure. Updated version -- with simplified notation -- accepted for publication in Phys.Rev.D. Extra author adde

Exact Hypersurface-Homogeneous Solutions in Cosmology and Astrophysics

A framework is introduced which explains the existence and similarities of most exact solutions of the Einstein equations with a wide range of sources for the class of hypersurface-homogeneous spacetimes which admit a Hamiltonian formulation. This class includes the spatially homogeneous cosmological models and the astrophysically interesting static spherically symmetric models as well as the stationary cylindrically symmetric models. The framework involves methods for finding and exploiting hidden symmetries and invariant submanifolds of the Hamiltonian formulation of the field equations. It unifies, simplifies and extends most known work on hypersurface-homogeneous exact solutions. It is shown that the same framework is also relevant to gravitational theories with a similar structure, like Brans-Dicke or higher-dimensional theories.Comment: 41 pages, REVTEX/LaTeX 2.09 file (don't use LaTeX2e !!!) Accepted for publication in Phys. Rev.