Antimicrobial activity and pharmacological behavior of cephaloglycine.
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Biomedical subjects
Publications and source records attributed to J Pitt.
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Two types of lymphoproliferative disease associated with Epstein-Barr viral (EBV) DNA--central-nervous-system lymphoma and chronic lymphocytic interstitial pneumonitis (LIP)--were recognised in children with human T-lymphotropic virus type III/lymphadenopathy virus infection and the acquired immunodeficiency syndrome (AIDS). Eight of ten lung biopsy specimens from children with LIP contained EBV DNA. EBV DNA was not identified in lung biopsy specimens with Pneumocystis carinii, cytomegalovirus, or atypical mycobacteria but without LIP, nor was EBV found in lung biopsy specimens from five adults with AIDS. Children with these EBV-associated complications had raised serum antibody titres to the replicative EBV antigens, but most of them lacked antibody to the component of the EB nuclear antigen encoded by the Bam HI K fragment. EBV-associated lymphoproliferative disease is a common and important complication of childhood AIDS.
PURPOSE: To evaluate saquinavir (SQV) pharmacokinetics, tolerance, and safety in 10 HIV-infected pregnant women between 14-32 weeks gestation. METHOD: This was a phase I, prospective, area-under-the-curve (AUC) targeted study. Antepartum treatment consisted of SQV 1200 mg tid, lamivudine 150 mg bid, and zidovudine 200 mg tid. The SQV targeted exposure was an 8-hour AUC (AUC(8)) of 3000 ng. h/mL; the study was to be halted if the first 4 participants did not achieve this AUC(8). Cord blood and plasma samples were collected in neonates at birth. RESULTS: Four women completed the SQV pharmacokinetic assessments. Exposure in all 4 patients was below the target AUC(8). Median (range) AUC(8) and trough (C8H) were 1672 (738-2614) ng. h/mL and 60 (<15-332) ng/mL, respectively. Oral clearance (CL/F) was 9.3 (5.1-16.6) L/h/kg and C(max) was 599 (177-953) ng/mL. Cord and neonate plasma concentrations were mostly undetectable; 1 of 5 infants was HIV-infected at 24 weeks. CONCLUSION: These data suggest highly variable SQV pharmacokinetics in pregnant women, and exposure at 1200 mg tid may not be adequate for longer term therapy; both the AUC(8) and C8H were considerably below average. Because ritonavir has been shown to significantly increase SQV concentrations, this combination should be further explored in this population.