Equivalencia terapéutica evaluada mediante estudios in vitro de medicamentos multifuentes: estudio de casos de amoxicilina, doxiciclina y fluconazol en Lima, Perú / Therapeutic equivalence evaluated by in vitro studies of multisource pharmaceutical products: case studies of amoxicillin, doxycycline and fluconazole in Lima, Peru

RESUMEN El objetivo del estudio fue determinar la equivalencia terapéutica evaluada mediante estudios in vitro de cuatro marcas de medicamentos conteniendo amoxicilina, doxiciclina y fluconazol adquiridos en establecimientos farmacéuticos de Lima Metropolitana y establecer su intercambiabilidad con un producto de referencia (PR). Se empleó un método validado de espectrofotometría ultravioleta visible para determinar el perfil de disolución. El factor de similitud (f2) se utilizó para establecer la equivalencia terapéutica, considerándose equivalentes si los valores de f2 se encontraban entre 50 y 100. Para doxiciclina los cuatro medicamentos fueron equivalentes in vitro al PR, para amoxicilina sólo dos medicamentos fueron equivalentes in vitro al PR y para fluconazol ninguno fue equivalente in vitro al PR. Se concluye que algunos medicamentos de amoxicilina y fluconazol que circulan en el mercado nacional no cumplen con la equivalencia terapéutica evaluada mediante estudios in vitro; es decir, no son intercambiables.

ABSTRACT The objective of the study was to determine the therapeutic equivalence evaluated through in vitro studies of four brands of drugs containing amoxicillin, doxycycline, and fluconazole purchased at pharmaceutical facilities in Metropolitan Lima, and to establish their interchangeability with a reference product (RP). A validated method of visible ultraviolet spectrophotometry was used to determine the dissolution profile. The similarity factor (f2) was used to establish the therapeutic equivalence, being considered equivalent if the values of f2 were between 50 and 100. For doxycycline, the four drugs were equivalent in vitro to the RP; for amoxicillin, only two drugs were equivalent in vitro to the RP; and for fluconazole, none was equivalent in vitro to the RP. It is concluded that some amoxicillin and fluconazole drugs circulating in the national market do not meet the therapeutic equivalence assessed by in vitro studies; in other words, they are not interchangeable.

Doxycycline release and antibacterial activity from PMMA/PEO electrospun fiber mats

Abstract Objective: To investigate the use of polymethyl methacrylate (PMMA) electrospun fiber mats containing different amounts of polyethylene oxide (PEO) as a doxycycline delivery system and to test antibacterial activity against an oral pathogen. Methodology: PMMA powders or PEO (mol wt 200 Kd) (10,20,30% w/w/) were dissolved in N, N-dimethylformamide (DMF) to obtain a final polymer concentration of 15% in DMF (w/v). 2% Doxycycline monohydrate was added to the solutions and submitted to vortex mixing. The solution was transferred to a plastic syringe and fit into a nanofiber electrospinning unit. The parameters applied were: voltage at 17.2 kV; distance of 20 cm between the needle tip and the collector plate; target speed at 2 m/min; and transverse speed at 1cm/min. Syringe pump speed was 0.15 mm/min. The drug release analysis was performed by removing aliquots of the drug-containing solution (in PBS) at specific periods. Doxycycline release was quantified using RP-HPLC. Fiber mats from all groups had their antibacterial action tested against S. mutans based on inhibition halos formed around the specimens. The experiments were performed in triplicate. Gravimetric analysis at specific periods was performed to determine any polymer loss. Morphological characterization of the electrospun fibers was completed under an optical microscope followed by SEM analysis. Results: The addition of PEO to the PMMA fibers did not affect the appearance and diameter of fibers. However, increasing the %PEO caused higher doxycycline release in the first 24 h. Fibers containing 30% PEO showed statistically significant higher release when compared with the other groups. Doxycycline released from the fibers containing 20% or 30% of PEO showed effective against S. mutans. Conclusion: The incorporation of PEO at 20% and 30% into PMMA fiber mat resulted in effective drug release systems, with detected antibacterial activity against S. mutans.

Actividad de metaloproteinasas de arterias y venas y su regulación mediante doxiciclina / Metalloproteinase activity of arteries and veins and it regulation through doxycicline

Segments of internal mammary arteries and saphenous veins and cultured smooth muscle cells were incubated with and without doxycicline. Metalloproteinases activity was assessed by zymography and Western Blot. Activity of Metalloproteinase-9 in saphenous veins was 217 percent less than in internal mammary arteries. In these vessels doxycicline decreased metalloproteinase-9 activity by 207 percent and metalloproteinase-1 expression. In cultured smooth muscle cells, the median inhibitory concentration of doxycicline for metalloproteinase-2 was 138 uM (r2=0.82). Internal mammary arteries and saphenous veins have different metalloproteinase activities, that are inhibited by doxycicline

Antipyrine and doxycycline pharmacokinetics in patients with thyroid disorders.

Pathological conditions are known to affect pharmacokinetics of many drugs. Antipyrine half-life is used as a marker of liver microsomal enzyme function. Antipyrine pharmacokinetics, therefore, was investigated in 23 thyrotoxic and 11 euthyroid goitre patients. Of these, 11 thyrotoxic and 9 euthyroid goitre patients also participated in doxycycline bioavailability studies. In thyrotoxic patients, antipyrine half-life and AUCo infinity and doxycycline Cpmax and AUCo infinity were found to be reduced as compared to those of healthy euthyroid normal subjects. Following treatment of thyrotoxicosis, the antipyrine half-life and AUCo infinity returned to normal. Doxycycline AUCo infinity returned to near normal range but Cpmax did not.