Abstract:We use the worldline formalism to derive integral representations for three classes of amplitudes in scalar field theory: (i) the scalar propagator exchanging N momenta with a scalar background field (ii) the "half-ladder" with N rungs in x-space (iii) the four-point ladder with N rungs in x-space as well as in (off-shell) momentum space. In each case we give a compact expression combining the N ! Feynman diagrams contributing to the amplitude. As our main application, we reconsider the well-known case of two massive scalars interacting through the exchange of a massless scalar. Applying asymptotic estimates and a saddle-point approximation to the N -rung ladder plus crossed ladder diagrams, we derive a semi-analytic approximation formula for the lowest bound state mass in this model.
Lopinavir (LPV), a newer HIV protease inhibitor, has poor bioavailability being a substrate of both cytochrome P450 3A enzyme system (CYP3A) and permeability-glycoprotein (P-gp). Ritonavir (RTV) is a known inhibitor of both P-gp and CYP3A and is co-administered with LPV in anti-HIV therapy. Grapefruit juice (GFJ) is known to inhibit CYP3A and has conflicting effects, ranging from activation to inhibition, on P-gp. In this research work, the effects of GFJ and RTV on the pharmacokinetics of LPV were compared in rats. A mechanistic evaluation was undertaken using various in vitro and ex vivo studies to support the in vivo pharmacokinetic data. The plasma levels of LPV were found to increase significantly upon co-administration with GFJ in single dose as well as multidose pretreatment studies. Similar, but marginally higher, results were observed upon co-administration of LPV with RTV. No significant change in t(max) was observed in the various treatment groups. The apparent permeability of LPV in the ileum increased significantly after the pre-incubation with GFJ and RTV compared with no pre-incubation. The GFJ and RTV showed a significant and similar inhibitory effect on rat intestinal microsomes in the metabolism of LPV. The GFJ was equally effective as RTV in increasing the bioavailability of LPV.
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