Vliv šesti antiretrovirotik (delavirdinu, stavudinu, lamivudinu, nelfinaviru, amprenaviru a lopinaviru/ritonaviru v kombinaci) na březí bílé krysy (Rattus norvegicus Albinus, Rodentia, Mammalia): biologický test

English version

Authors: M. U. Nakamura ^*; Edward Araujo Júnior ^*; Simões M. J.+; Oliveira Filho R. M.§; L. Kulay Júnior ^*
Authors‘ workplace: Department of Obstetrics, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil +Department of Morphology, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil §Department of Pharmacology, São Paulo University (USP), São Paulo, SP, ^*
Published in: Ceska Gynekol 2014; 79(4): 295-304

Overview

Cíl:
Srovnat chronické účinky antiretrovirotické léčby (lamivudin, stavudin, delavirdin, nelfinavir, amprenaviru a kombinace lopinaviru/ritonaviru) u březích potkanů albínů.

Typ studie:
Review.

Název a sídlo pracoviště:
Gynekologicko-porodnická klinika, Federal University of São Paulo (UNIFESP), Sao Paulo, SP, Brazílie.

Metodika:
Retrospektivní srovnávací studie se zabývala 18 skupinami po 10 březích samičkách potkanů, které byly téměř tři měsíce staré a vážily 200 gramů. Každé z nich byla denně aplikována léčba pomocí žaludeční sondy, zatímco kontrolní skupině byl aplikován 1 ml destilované vody. Studijní skupiny obdržely lamivudin (5, 15 a 45 mg/kg/den); stavudin (na 1, 3 a 9 mg/kg/den); nelfinavir (40, 120 a 360 mg/kg/den); amprenavir (na 46, 138 a 414 mg/kg/den); lopinavir/ritonavir (12.8/3.2, a 38.4/9.6 115/28.8 mg/kg/den) a delavirdin (20 a 60 mg/kg/den). To představuje jedno-, troj- a devítinásobek terapeutické dávky pro člověka, s výjimkou posledního léku, kde nebyla nejvyšší dávka podána. Byla hodnocena hmotnost samice, plodu a placenty, počet implantací a reabsorpcí, hlavní zevní malformace plodu a odumření samice nebo plodu. Pro statistické zpracování byly použity test Kruskalův-Wallisův a χ2 test.

Výsledky:
U všech tří dávek stavudin zvyšoval hmotnost samice (p = 0,001), zatímco lamivudin při trojnásobné a devítinásobné dávce hmotnost snižoval (p < 0,001). Amprenavir u všech dávek, a lopinavir//ritonavir u troj- a devítinásobné dávky zvyšoval úmrtnost samic (p < 0,001). Z hlediska plodů nebylo žádné z antiretrovirotik škodlivé, pokud jde o implantaci, reabsorpci, teratogenitu a úmrtnost (p > 0,05). Stavudin při všech dávkách snižoval hmotnost mláďat(p < 0,001); Nicméně lamivudin u trojnásobné, delavirdin u trojnásobné a amprenavir u trojnásobné dávky hmotnost mláďat zvyšoval (p < 0,001).

Závěr:
U březích samic jsme pozorovali letální toxicitu u krys, kterým byl aplikován amprenavir a ritonavir/lopinavir; hmotnost krys se měnila při užití lamivudinu a stavudinu . U plodů byly pozorovány nežádoucí účinky v souvislosti s hmotností mláďat u stavudinu, lamivudinu, amprenaviru a delavirdinu..

Klíčová slova:
březí krysy, antiretrovirotika, teratologie, biologický test

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