ABSTRACT
The study analyzed the effect of mannitol on the pharmacokinetics (PK) of amikacin. Adult Wistar rats were treated as follows: Group 1 (G1) received mannitol for three days, Group 2 (G2) received mannitol plus 10 mg/kg of amikacin simultaneously, and Group 3 only amikacin. The PK study was conducted on the 4th day. For which, blood samples were drawn at fixed times during 24 h and immunoenzymatically analyzed. Results revealed significant differences (p<0.05) between the groups, e.g. Cmax were 62.26 ± 15.75 µg/ml for G1, 72.63 ± 24.80 µg/ml for G2 and 68.61 ± 27.40 µg/ml for G3. The AUC also differed in the three groups, being largest for G2, 222.52 ± 47.30 µg/ml/h, and smallest for G1, 135.59 ± 39.00 µg/ml/h. Alteration of the PK parameters observed between the groups must be considered when both drugs are prescribed, although human studies are necessary to confirm the results.
O estudo analisa o efeito do manitol na farmacocinética (PK) da amicacina . Ratos adultos Wistar foram tratadas da seguinte maneira: o grupo 1 (G1) recebeu manitol durante três días. Ao grupo 2 (G2) se administrou manitol e 10 mg/kg de amicacina, ao mesmo tempo. Finalmente, o grupo 3 (G3) recebeu somente amicacina. No quarto día se realizou o estudo de PK nos três grupos. Para isso, foram retiradas amostras de sangue, em tempos pre-determinados, durante 24 horas, que foram analisadas por métodos imunoenzimáticos. Os resultados mostraram diferencas significativas (p < 0.05) entre os grupos. Po exemplo, os valores obtidos de Cmax foram 62.26 ± 15.75 µg/ml para G1, 72.63 ± 24.80 µg/ml para G2 e 68.61 ± 27.40 µg/ml para o Grupo 3. A AUC foi também diferente entre os três grupos: a maior para G2, com, 222.52 ± 47.30 µg/ml/h, e a menor para G1, com um valor de 135.59 ± 39.00 µg/ml/h. A alteração dos parámetros de PK entre os grupos debe ser considerada quando se administram os dois farmacos simultaneamente. No entanto, é necessario realizar estudos em seres humanos para confirmar os nossos resultados.
ABSTRACT
Propafenone is an effective antiarrhythmic agent used in children, while in Mexico no specific formulation for children is available, which causes errors in adequate dosage. The aim of this study was to determine the bioavailability of a suspension prepared extemporaneously using commercial tablets of propafenone. The bioavailability was determined in two groups of rabbits (n = 8): the first group received a single intravenous dose of 2 mg/kg of propafenone; the second was orally administered an extemporaneous suspension of propafenone prepared from commercial tablets. Blood samples were drawn at several times during the next 24 h and analysed by HPLC to determine drug levels. The extemporaneous suspension was tested previously with satisfactory results regarding physicochemical and microbiologic stability. The area under the curve (AUC) for the i.v. route was 5600.6 ng/ml.h and for oral administration the AUC was 3327.6 ng/ml.h. The bioavailability was calculated at 59.41%. These results are consistent with previous reports for solid dosage forms. The propafenone suspension prepared extemporaneously using commercial tablets is bioavailable using an animal model; nevertheless, it is necessary to carry out human studies either in volunteers or in patients to confirm these results.
