No abstract

In drug-drug interaction (DDI) research, a two drug interaction is usually predicted by individual drug pharmacokinetics (PK). Although subject-specific drug concentration data from clinical PK studies on inhibitor/inducer or substrate's PK are not usually published, sample mean plasma drug concentrations and their standard deviations have been routinely reported. In this paper, an innovative DDI prediction method based on a three-level hierarchical Bayesian meta-analysis model is developed. The first level model is a study-specific sample mean model; the second level model is a random effect model connecting different PK studies; and all priors of PK parameters are specified in the third level model. A Monte Carlo Markov chain (MCMC) PK parameter estimation procedure is developed, and DDI prediction for a future study is conducted based on the PK models of two drugs and posterior distributions of the PK parameters. The performance of Bayesian meta-analysis in DDI prediction is demonstrated through a ketoconazole-midazolam example. The biases of DDI prediction are evaluated through statistical simulation studies. The DDI marker, ratio of area under the concentration curves, is predicted with little bias (less than 5 per cent), and its 90 per cent credible interval coverage rate is close to the nominal level. Sensitivity analysis is conducted to justify prior distribution selections.

The achievement of room-temperature (300 °K) operation of Ga(1−x)AlxAs-GaAs double-heterostructure lasers with active layers of quantum-well dimensions ∼200 Å thick is reported. These devices are grown by metalorganic chemical vapor deposition and exhibit pronounced effects in the spectral and lasing characteristics that are related to the small active region thickness and are the first such effects observed for DH lasers in the GaAlAs-GaAs system.

GaAlAsSb heterostructure low leakage photodiodes have been fabricated. These devices exhibit leakage currents of 7 to 9 nA (25–35 μA/cm2) and capacitances of approximately 1 pF at 20-V reverse bias. The devices are planar Be-implanted structures and have a net donor concentration of 2×1015 cm−3 in Ga1−xAlxAsSb (x∼0.15).