Drugs online research references
Antimicrob Agents Chemother. 1992 May;36(5):1013-8.
Once-a-week azithromycin in AIDS patients: tolerability, kinetics, and effects on zidovudine disposition.
Chave JP, Munafo A, Chatton JY, Dayer P, Glauser MP, Biollaz J.
Departement de Medecine Interne, Centre Hospitalier, Universitaire Vaudois, Lausanne, Switzerland.
Toxoplasmic encephalitis is one of the leading causes of morbidity in patients with AIDS. Lifelong treatment is needed to prevent relapses, and primary prevention is desirable in high-risk patients, but the available drugs are often poorly tolerated. Azithromycin (AZM) has been considered a drug candidate because of its efficacy in the animal model and its kinetic properties, which would allow intermittent administration. The tolerability and kinetics of AZM and its effect on the disposition of zidovudine (ZVD) were therefore evaluated in a preliminary open study in nine human immunodeficiency virus-infected patients. AZM was administered once weekly for 5 weeks 2 h before the usual morning ZVD dose. The day before and on the first and fifth AZM dosings, blood samples were drawn every 30 min during 5 h for determination of the concentrations of ZVD and its glucuronide metabolite. Blood samples were drawn for AZM measurement over 72 and 360 h on the first and fifth AZM administrations, respectively, as well as before and 3 h after dosing on the second, third, and fourth AZM dosings. After the first and fifth administrations, maximum AZM concentrations in serum were 0.6 +/- 0.1 and 0.8 +/- 0.2 microM (mean +/- standard error of the mean), respectively; times to peak concentration in serum were 3.7 +/- 0.2 and 2.9 +/- 0.4 h, respectively; areas under the plasma concentration-time curves were 9.2 +/- 1.6 and 9.3 +/- 2.0 micrograms.h/ml, respectively; and half-lives were 61.0 +/- 5.4 and 63.8 +/- 6.7 h, respectively. On days -1, 1, and 29, ZVD kinetic parameters were as follows: maximum concentrations in serum, 3.1+/- 0.6, 4.3 +/- 0.6, and 4.2 +/- 0.9 microM, respectively; times to maximum concentrations in serum, 1.1 +/- 0.4, 0.8 +/- 0.2, and 1.2 +/- 0.3 h, respectively: areas under the plasma concentration-time curves, 5.3 +/- 0.9, 5.9 +/- 0.6, and 5.7 +/- 0.8 microgram . h/ml, respectively; and half-lives, 1.3 +/- 0.08, 1.4 +/- 0.04, and 1.3 +/- 0.04 h, respectively. Except for transient mild abdominal cramps that occurred at 2 to 3 h postdose (6 of 45 exposures) and nausea (4 of 45 exposures), neither subjective nor objective side effects were observed. The kinetics of AZM were similar after the first and repeated administrations, and the disposition of ZVD was not altered by this treatment. The efficacy of AZM in preventing cerebral toxoplasmosis can therefore be safely tested in human immunodeficiency virus-infected patients concomitantly treated with zidovudine.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1324635&dopt=Abstract
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Antimicrob Agents Chemother. 1992 May;36(5):997-1001.
Synergistic activity of azithromycin and pyrimethamine or sulfadiazine in acute experimental toxoplasmosis.
Derouin F, Almadany R, Chau F, Rouveix B, Pocidalo JJ.
Laboratoire de Parasitologie-Mycologie, Hopital Saint-Louis, Paris, France.
The efficacy of azithromycin administered alone or combined with pyrimethamine or sulfadiazine was examined in a murine model of acute toxoplasmosis. Outbred Swiss mice acutely infected with tachyzoites of the virulent RH strain were treated for 10 days from day +1 postinfection. The efficacy of each regimen was assessed in terms of survival rates and sequential titration of parasites in blood, brain, and lungs by using a tissue culture method. Administration of azithromycin at 300, 150, or 75 mg/kg of body weight per day resulted in prolonged survival relative to that of untreated controls; sequential examination of parasite burden showed early eradiaction of Toxoplasma gondii from the lungs, whereas dissemination to the brain was not prevented. A remarkable synergistic effect was observed when azithromycin (150 mg/kg/day) was administered in combination with pyrimethamine or sulfadiazine at noncurative dosages, i.e., 12.5 and 200 mg/kg/day, respectively. In mice treated with azithromycin plus sulfadiazine and azithromycin plus pyrimethamine, parasite burdens in blood and organs, relapses after cessation of therapy, and mortality were all markedly reduced relative to mice treated with any of the agents alone. These results show that azithromycin, which is remarkably active on pulmonary Toxoplasma infection, significantly potentiates the curative effect of sulfadiazine or pyrimethamine.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1324642&dopt=Abstract
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Antimicrob Agents Chemother. 1992 Jul;36(7):1412-7.
Activity and local delivery of azithromycin in a mouse model of Haemophilus influenzae lung infection.
Vallee E, Azoulay-Dupuis E, Pocidalo JJ, Bergogne-Berezin E.
Institut National de la Sante et de la Recherche Medicale U 13, Paris, France.
We compared the activities of azithromycin and erythromycin against Haemophilus influenzae in a mouse model of nonparenchymatous lower respiratory tract infection. In vitro and in vivo efficacy data for both drugs were analyzed relative to their pharmacokinetics in lungs and in vivo uptake by phagocytes. Aged C57BL/6 mice (mean age, 15.1 +/- 1.9 months) were infected intratracheally with 10(8) CFU of H. influenzae serotype b. Oral drug administration was initiated 4 h after infection by various dosage regimens. In terms of bacterial killing in the lung, azithromycin was much more active than erythromycin (P less than 0.01). Its in vivo activity was also more durable after a single administration relative to the durability of three doses of erythromycin given at 6-h intervals. The MIC of azithromycin was eightfold lower than that of erythromycin, and better penetration and a longer half-life in lung tissue were achieved after a single oral administration. Phagocytes delivered increased amounts of both drugs to the infected lungs, particularly at the site of infection (bronchoalveolar airspaces), and detectable levels of azithromycin were maintained locally for long periods. The fact that the efficacy of azithromycin coincided with the arrival of large numbers of polymorphonuclear leukocytes within the airspaces suggests that active extracellular concentrations were provided by the release of azithromycin from these cells. This further supports the potential value of once-daily azithromycin regimens for the treatment of lower respiratory tract infections in humans, provided that inhibitory concentrations against common pathogens such as H. influenzae are maintained for adequate periods of time.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1324644&dopt=Abstract
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