ritonavir and Urinary-Calculi

Topics: Anti-Retroviral Agents; Atazanavir Sulfate; Dideoxynucleosides; Drug Therapy, Combination; HIV Infections; Humans; Lamivudine; Male; Middle Aged; Oligopeptides; Pyridines; Ritonavir; Uric Acid; Urinary Calculi; Urolithiasis

We report here the first case to add amprenavir to the growing list of antiretroviral drugs associated with urinary stones. The first reported case of a nelfinavir urinary stone was reported in 2002 in a 37-year-old HIV-infected woman. In September 2007, the same female patient was referred to our department with recent onset of right flank pain and recurrent urinary tract infections. Abdominal computed tomography revealed three obstructing stones in the distal right ureter, another stone in the right renal pelvis with hydronephrosis and a stone in the left kidney. After stone retrieval, analysis of the stone by liquid chromatography with mass spectrometry revealed a stone composition of 95% unmodified amprenavir and 5% ritonavir.

Topics: Adult; Anti-HIV Agents; Carbamates; Female; Furans; HIV Infections; HIV Protease Inhibitors; Humans; Ritonavir; Sulfonamides; Tomography, X-Ray Computed; Urinary Calculi

Recent results from human clinical trials have established the critical role of HIV protease inhibitors in the treatment of acquired immune-deficiency syndrome (AIDS). However, the emergence of viral resistance, demanding treatment protocols, and adverse side effects have exposed the urgent need for a second generation of HIV protease inhibitors. The continued exploration of our hydroxylaminepentanamide (HAPA) transition-state isostere series of HIV protease inhibitors, which initially resulted in the identification of Crixivan (indinavir sulfate, MK-639, L-735,524), has now yielded MK-944a (L-756,423). This compound is potent, is selective, and competitively inhibits HIV-1 PR with a K(i) value of 0.049 nM. It stops the spread of the HIV(IIIb)-infected MT4 lymphoid cells at 25.0-50.0 nM, even in the presence of alpha(1) acid glycoprotein, human serum albumin, normal human serum, or fetal bovine serum. MK-944a has a longer half-life in several animal models (rats, dogs, and monkeys) than indinavir sulfate and is currently in advanced human clinical trials.

Topics: Animals; Antiviral Agents; Cattle; Cell Culture Techniques; Dogs; Drug Evaluation, Preclinical; Drug Resistance, Microbial; Haplorhini; HIV Protease Inhibitors; HIV-1; Humans; Indans; Male; Piperazines; Protein Binding; Rats; Rats, Sprague-Dawley; Structure-Activity Relationship; Urinary Calculi