Lopinavir protein binding in HIV‐1‐infected pregnant women

Background

Pregnancy may alter protein binding (PB) of highly bound protease inhibitors due to changes in plasma concentrations of albumin and α‐1 acid glycoprotein (AAG). Small changes in PB can greatly impact the fraction of drug unbound (FU) exerting pharmacological effect. We report lopinavir (LPV) PB during third trimester (antepartum, AP) compared to ≥1.7 weeks postpartum (PP) to determine if FU changes compensate for reduced total concentrations reported previously.

Methods

P1026s enrolled women receiving LPV/ritonavir, soft gel capsules 400/100 mg or 533/133 mg twice daily. LPV FU, albumin and AAG were determined AP and PP.

Results

AP/PP samples were available from 29/25 women respectively with all but one woman receiving the same dose AP/PP. LPV FU was increased 18% AP vs. PP (mean 0.96±0.16% AP vs. 0.82±0.21% PP, P=0.001). Mean protein concentrations were reduced AP (AAG=477 mg/L; albumin=3.28 mg/dL) vs. PP (AAG=1007 mg/L; albumin=3.85 mg/dL) (P<0.0001 for each comparison). AAG concentration correlated with LPV binding. Total LPV concentration did not correlate with LPV FU AP or PP. However, higher LPV concentration PP was associated with reduced PB and higher FU after adjustment for AAG.

Conclusions

LPV FU was higher and AAG lower AP vs. PP. The 18% increase in LPV FU AP is smaller than the reduction in total LPV concentration reported previously and is not of sufficient magnitude to eliminate the need for an increased dose during pregnancy.

     

Enzyme leakage, trypsinogen activation, and inflammatory response in endoscopic retrograde cholangiopancreatography-induced pancreatitis

INTRODUCTION: Endoscopic retrograde cholangiopancreatography (ERCP)-induced pancreatitis (EIP) provides an opportunity to study different pathophysiologic events early in the course of acute pancreatitis. AIMS: To investigate whether the leakage of pancreatic proenzymes (anionic trypsinogen), pancreatic protease activation (carboxypeptidase B activation peptide), cytokine response (interleukin [IL]-1 receptor antagonist, IL-6, and soluble tumor necrosis factor receptor-I) and neutrophil activation (neutrophil gelatinase-associated lipocalin and polymorphonuclear elastase) differ between patients with and without EIP. A second aim was to clarify the temporal relation between these different events. METHODOLOGY: Ninety-nine nonconsecutive patients undergoing ERCP were investigated in the study. RESULTS: Fourteen of 99 patients undergoing ERCP developed mild EIP. Six hours after the investigation the concentration of anionic trypsinogen was significantly higher in patients with EIP than in patients without EIP. The day after ERCP, higher concentrations of anionic trypsinogen, carboxypeptidase B activation peptide, IL-6, and polymorphonuclear elastase were recorded in the EIP group. No significant differences in IL-1 receptor antagonist, soluble tumor necrosis factor receptor-I or neutrophil gelatinase-associated lipocalin were found between the groups in this study. CONCLUSION: Mild EIP was accompanied by early leakage of proenzymes and later activation of trypsinogen/proteases. A significant cytokine response and neutrophil activation were recorded the day after ERCP, but further studies are needed to determine the temporal relation between these different pathophysiologic events.     

An alternative approach to the inaccessible intradiverticular papilla.

BACKGROUND: In patients with a narrow-necked juxtapapillary diverticulum the endoscopic cannulation of the papilla of Vater and the subsequent biliary therapy is sometimes impossible. PATIENTS AND METHODS: Three patients referred for endoscopic retrograde cholangiography and stone extraction were included. Earlier attempts to cannulate failed because visual control was impeded by narrow-necked juxtapapillary diverticula with the papilla located in the fundus. Endoscopic balloon dilation of the narrow diverticular neck, using a 15-mm stone retrieval balloon, was carried out. RESULTS: In all three cases the papillary orifice was readily brought into view after balloon dilation of the diverticular opening. Subsequent endoscopic treatment to the bile duct was successful without any complications. CONCLUSION: Balloon dilation of a narrow-necked juxtapapillary diverticulum is a safe and easy procedure, which facilitates both cannulation of the papilla and subsequent biliary endoscopic treatment.