De metadona a buprenorfina. La inducción del tratamiento / From methadone to buprenorphine. Treatment induction

Objetivo: La inducción de buprenorfina en pacientes en tratamiento con metadona es una parte fundamental del tratamiento y va a condicionar la continuidad y retención posterior. Esto se debe a sus características farmacológicas, mayor afinidad por los receptores opiáceos que la metadona pero menor actividad intrínseca sobre ellos.Cuando los pacientes en mantenimiento con metadona toman una dosis de buprenorfina se desplaza la metadona que queda en los receptores opiáceos precipitando síntomas de abstinencia.Material y métodos: se analiza el proceso de la inducción con buprenorfina en pacientes en programas de mantenimiento con metadona.Resultados: El objetivo de esta fase es encontrar la dosis mínima de buprenorfina con la que el paciente se encuentre bien, sin deseo de consumo ni síntomas de abstinencia.Conclusiones: El clínico debe tener en cuenta una serie de parámetros al plantearse la transición como determinar el tiempo de espera adecuado para la transición basado en la dosis y la concentración plasmática de metadona previa al cambio, evaluación de síntomas de abstinencia en los diferentes momentos del proceso de inducción, consumo de otros opiáceos, dosificación adecuada de buprenorfina e información a los pacientes (AU)

Differential serological testing by simultaneous indirect immunofluorescent antibody test in canine leishmaniosis and ehrlichiosis.

A mixed indirect fluorescence antibody test (IFAT), based on cultured promastigotes Leishmania infantum and formol-inactivated suspension of cells infected with the bacteria Ehrlichia canis, was applied to make a differential diagnosis between canine ehrlichiosis and leishmaniosis. A titre greater than 80 was considered positive for antibodies to E. canis and suggestive of antibodies to L. infantum. Positive sera were titrated subsequently by serial dilutions to confirm antibodies positive to Leishmania and establishing the antibody titre of both pathogens. Fluorescence was absent with negative control sera and background staining was minimal. No serological cross-reactions between positive sera for L. infantum or E. canis were detected. Results obtained by mixed IFAT did not differ when the same serum IFAT standard was compared. The test showed equivalent sensitivity (100%). The specifities were 100% for L. infantum and 98.5% for E. canis. The equivalence in sensitivity was confirmed by calculating the correlation coefficient between IFAT standards and mixed IFAT (r>or=0.99 for both pathogens). The results of our investigations demonstrated that mixed IFAT is a specific means of establishing serological differential diagnosis of canine leishmaniosis and ehrlichiosis.

[Nevirapine induces abstinence symptoms in patients on a methadone maintenance program with HIV infection]. / La nevirapina induce síntomas de abstinencia en pacientes en programa de mantenimiento con metadona con infección por VIH.

The objective of this study was to investigate the potential inductive effect of nevirapine (NVP) with methadone. Eight patients on the methadone maintenance programme with anti-retroviral therapy because of their infection with HIV, well maintained with methadone and without symptoms of abstinence were studied. All were included in a study of measurement of plasma levels of methadone. Anti-retroviral medication was changed, including NVP, and patients began with symptoms of abstinence 5 to 10 days later. Our results indicate an inductive effect of NVP on the methadone metabolism which caused symptoms of abstinence in all patients, which prompted an increase in the dose and plasma concentration of methadone was lost; patients continued with significantly low plasma levels (p < 0.01) after a therapy mean duration of 6.5 months, with no full recovery.

La nevirapina induce síntomas de abstinencia en pacientes en programa de mantenimiento con metadona con infección por VIH / Nevirapine induces abstinence symptoms among HIV-infected patients on a methadone maintenance programme

El objetivo de nuestro estudio fue investigar el posible efecto inductor de la nevirapina (NVP) con la metadona. Estudiamos ocho pacientes en programa de mantenimiento con metadona con tratamiento antirretrovírico por su infección por virus de la inmunodeficiencia humana, bien mantenidos con metadona y sin síntomas de abstinencia a opiáceos. Todos estaban incluidos en un estudio de medición de niveles plasmáticos de metadona. Se les cambió la medicación antirretrovírica, incluyendo NVP, y comenzaron con síntomas de abstinencia entre los cinco y los diez días posteriores. Nuestros resultados indican un efecto inductor de la NVP en el metabolismo de la metadona que produjo síntomas de abstinencia en todos ellos, obligando a subir las dosis y perdiendo su concentración plasmática de metadona; continuaron con niveles en plasma significativamente bajos (p < 0,01) tras una media de tratamiento de 6,5 meses, sin llegar a recuperarse (AU)

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Methimazole-mediated enhancement of albendazole oral bioavailability and anthelmintic effects against parenteral stages of Trichinella spiralis in mice: the influence of the dose-regime.

The influence of methimazole (MTZ) inhibitor of the microsomal oxidases on the systemic availability of the albendazole sulpho-metabolites (ABZS-MT) albendazole-sulphoxide (ABZSO) and albendazole-sulphone (ABZSO2) and on its anthelmintic effects was investigated in a mouse model for helminthic infections. Plasma concentrations of the ABZS-MT were measured by high performance liquid chromatography (HPLC) following treatment of Swiss CD-1 mice with albendazole (ABZ) alone or ABZ plus MTZ, at both single and repeated doses. The anthelmintic effects were assessed in age-matched mice similarly treated following infection with Trichinella spiralis. MTZ significantly (p < 0.01) increased the ABZS-MT plasma concentrations although the pharmacokinetic profile varied greatly according to the dose of ABZ administered. When ABZ was given at a single dose of 50 mg/kg followed by MTZ at 3 mg/kg, a cumulative effect was observed in the ABZS-MT plasma levels with pharmacokinetic parameters (Tmax = 24 h, Cmax= 30.88 microg/ml and AUC = 1120.80 microg h/ml) significantly ( p < 0.01) higher than those following administration of ABZ alone (Tmax = 3 h, Cmax = 11.00 microg/ml and AUC = 268.03 microg h/ml). This cumulative effect was absent following administration of ABZ at 100 mg/kg where, after reaching a maximum (Cmax = 27.23 microg/ml) at 3 h post-administration (Tmax), the ABZS-MTplasma levels felt down quickly to values under those obtained after administration of ABZ at the same dose, but alone (AUC = 362.15 microg h/ml vs. 340.15 microg h/ml, respectively). When ABZ was given at 50 mg/kg together with MTZ three times every 24 h, a rapid decrease was observed in the ABZS-MT plasma levels following administration of both the second and third doses, respectively. The pharmacokinetic profile of ABZS-MT following administration of each of the three doses of ABZ at 100 mg/kg plus MTZ was the same as that obtained after the single treatment. The rapid decrease of the ABZS-MT plasma levels observed after the sustained treatment or after the single treatment at 100 mg/kg could be due to a microsomal oxidase inductive effect (probably the cytochrome P-450) caused by ABZSO. The co-administration of MTZ significantly (p < 0.01) increased the anthelmintic effects of ABZ against both migrating and encysted larvae of T. spiralis. Repeated treatment did not improve the anthelmintic effects of the single treatment as the efficacies against both stages of the parasite were always lower or identical to those of the single treatment at the corresponding doses.

Albendazole versus ricobendazole (albendazole-sulphoxide) against enteral and parenteral stages of Trichinella spiralis in mice.

Comparison of the anthelmintic activity and pharmacokinetic profiles following albendazole (ABZ) and albendazole-sulphoxide (ricobendazole = RBZ) administration was made in a mouse model for helminthic infections. Swiss CD-1 mice were experimentally infected with Trichinella spiralis and treated with either ABZ or RBZ at 3 different stages of the parasite life-cycle: pre-adult (day 1 p.i.), migrating larvae (days 13, 14 and 15 p.i.) and encysted muscle larvae (days 34, 35 and 36 p.i.). Plasma concentrations of albendazole-sulphoxide (ABZSO) were measured in age matched non-infected mice by high performance liquid chromatography (HPLC), after administration of ABZ or RBZ dosed at 50 mg ABZ equivalent kg-1. ABZSO pharmacokinetic profiles following ABZ or RBZ administration were similar, although the Tmax (1.83 +/- 0.30 and 0.41 +/- 0.28, respectively) were significantly different (P < 0.01). Against pre-adult stages ABZ was significantly (P < 0.05) more effective than RBZ when administered at 10 mg kg-1 (96.5% and 78.0% reduction with respect to the control group). Migrating and encysted larvae were less sensitive to both compounds and dose rates had to be increased to 100 mg kg-1 to achieve significant efficacies. Against parenteral stages, ABZ was significantly more effective than RBZ when both were given at 100 mg kg-1 (64.0% and 44.2% reduction against migrating larvae and 94.7% and 65.5% reduction against encysted larvae, respectively). In conclusion, RBZ was not more effective than ABZ against enteral and parenteral stages of Trichinella spiralis.

Anthelmintic activity of 6,7-diaryl-pteridines.

In a search for new anthelmintic compounds, some 6,7-diaryl-pteridines were synthesized from the corresponding diaminopyrimidines and aromatic aldehydes. Their anthelmintic activity was tested in vitro against Caenorhabditis elegans and Heligmosomoides polygyrus and in vivo against Trichinella spiralis. Structure-activity relationships are discussed.