Karwinskia humboldtiana (buckthorn) fruit causes central nervous system damage during chronic intoxication in the rat.

Karwinskia humboldtiana fruit (Kh) causes a neurological disorder 3-4 weeks after ingestion, characterized by flaccid, symmetrical, ascending paralysis, similar to the Guillain-Barre syndrome. In this polyneuropathy the lesion (demyelization) in peripheral nerves has been described in several animal species, both in acute and in chronic intoxication. However, no reports exist about the presence of lesions in the Central Nervous System (CNS), in chronic intoxication. We considered it important to evaluate, with histological techniques, the possible presence of lesions in the brain, by using a model of chronic intoxication that reproduces the same stages present in the human intoxication, to better understanding of this pathological process. In our present work we fed the ground Kh fruit to Wistar rats and samples of brain, cerebellum, and pons were embedded in paraffin. Sections were stained with Hematoxylin & Eosin (HE) and special stains for nerve tissue. Histopathological changes were evaluated in the CNS through the different stages of the polyneuropathy and comparison to a control group. With this methodology, we found lesions in the motor pathway. This is the first report about the presence of neuronal damage caused by Kh in the Central Nervous System in chronic intoxication.

Bioequivalence of single 100-mg doses of two oral formulations of topiramate: an open-label, randomized-sequence, two-period crossover study in healthy adult male Mexican volunteers.

BACKGROUND: The proprietary form of topiramate is indicated in Mexico as an antiepileptic agent and in the prophylaxis of migraine headaches. However, before generic topiramate is placed on the market, pharmacokinetic studies investigating the bioequivalence of generic and branded formulations are needed. OBJECTIVE: The aim of this study was to compare the bioequivalence and tolerability of a generic (test) and a branded (reference) formulation of topiramate 100 mg in healthy Mexican volunteers. METHODS: This open-label, randomized-sequence, 2-period crossover study was conducted at Ipharma SA de CV, Monterrey, Mexico. Eligible subjects were healthy male Mexican volunteers aged 18 to 45 years. Participants were randomly assigned to receive 100 mg of the test or reference formulation, followed by a 3-week washout period and administration of the alternate formulation. Doses were administered after a 12-hour overnight fast. For analysis of pharmacokinetic properties, including C(max), AUC(0-t), and AUC(0-infinity), blood samples were obtained over a 144-hour period after dosing. The formulations were to be considered bioequivalent if calculations of a 90% CI for the ratio of the means of the measures for the test and reference formulations fell within bioequivalence limits, 80% to 125%, for logarithmic (log) transformation of C(max) and AUC, and if two 1-sided t tests showed P < 0.05. Tolerability was assessed using vital sign measurement (blood pressure, body temperature, heart rate, and respiratory rate), laboratory analysis (hematology, blood biochemistry, hepatic function, and urinalysis), and subject interview. RESULTS: Twenty-eight men (mean age, 22.21 years [range, 18-28 years]; mean weight, 75.04 kg [range, 62-96 kg]; mean height, 177 cm [range, 163-192 cm]) were enrolled in this study, and 28 (14 each randomized to receive the test or reference formulation first) completed it. No period or sequence effects were observed. The 90% CIs for the log-transformed C(max), AUC(0-t) and AUC(0-infinity) were 94.70 to 112.05, 98.88 to 105.16, and 98.80 to 105.28, respectively (all, P < 0.05). No adverse events were reported by the volunteers or found on clinical laboratory testing during the study. CONCLUSIONS: This study did not find any statistically significant differences in C(max) or AUC values between the test and reference formulations of oral topiramate 100 mg in this population of healthy adult male Mexican volunteers. On that basis, and according to both the rate and extent of absorption, the test and reference formulations met the regulatory criteria for bioequivalence. Both formulations were well tolerated.

Evaluation of the bioequivalence of single 100-mg doses of two oral formulations of cyclosporin A microemulsion: a randomized, open-label, two-period crossover study in healthy adult male Mexican volunteers.

BACKGROUND: Cyclosporin A is widely used in Mexico as immunosuppressive therapy in organ transplantation and in the treatment of autoimmune disorders. Although several generic oral formulations of cyclosporin A are available in Mexico, information concerning the bioequivalence of these formulations in the Mexican population is not available in the published literature. OBJECTIVE: The aim of this study was to compare the bioequivalence and tolerability of a generic (test) and a branded (reference) soft-gelatin capsule formulation of cyclosporin A microemulsion 100 mg available in Mexico. METHODS: This randomized, open-label, 2-period cross-over study was performed at the Universidad Autónomade Nuevo León, Monterrey, México. Eligible subjects were healthy male volunteers who were randomly assigned to receive a single 100-mg dose of the test or reference formulation, followed by a 2-week washout period and administration of the alternate formulation. Doses were administered after a 12-hour overnight fast. For analysis of pharmacokinetic properties, including C(max), AUC(0-t), and AUC(0-infinity) , blood samples were obtained at intervals over the 48-hour period after dosing. The formulations were considered bioequivalent if the log-transformed ratios of Cma x and AUC were within the predetermined equivalence range (80%-125%). Tolerability was assessed by monitoring vital signs and laboratory tests (hematology, blood biochemistry, hepatic function, and urinalysis), and by questioning subjects about adverse events. RESULTS: Thirty-six male subjects (mean age, 22.08 years [range, 18-29 years]; mean weight, 78.23 kg [range, 72-89 kg]; mean height, 177 cm [range, 169-185 cm]) were enrolled in the study, and 34 (17 each randomized to receive the test or reference formulation first) completed it. No period or sequence effect was observed. The 90% CIs for the log-transformed ratios of C(max), AUC(0-t), and AUC(0-infinity) were 85.12 to 92.85, 92.14 to 99.75, and 92.19 to 99.72, respectively (all, P <0.05). Similar results were found for the data without log-transformation. No adverse events occurred or were reported by patients during the study. CONCLUSIONS: In this small study in healthy adult male Mexican volunteers, a single 100-mg dose of the test formulation was bioequivalent to a single 100-mg dose of the reference formulation based on the regulatory definition (rate and extent of absorption). Both formulations were well tolerated.

An experimental model of peripheral neuropathy induced in rats by Karwinskia humboldtiana (buckthorn) fruit.

Intoxication by Karwinskia humboldtiana (buckthorn) fruit presents a neurological picture similar to that of Guillain-Barré syndrome. In this report, we describe an experimental animal model of peripheral neuropathy induced by buckthorn fruit. Four groups of Wistar rats received one oral dose of 1.5 g/kg followed by oral doses of 0.5 g/kg at days 3, 7, 10, and 14 of dried and ground buckthorn fruit in aqueous suspension. Rats were sacrificed at 24, 48, 58, and 112 days after initial dose. Treated animals developed progressive paralysis through 58 days, then completely recovered by 112 days. Sciatic nerves showed segmental demyelination and cellular infiltrates until 58 days after exposure and then remyelinating changes at 112 days. This experimental model for peripheral neuropathy is reproducible and easy to handle. Its manipulation is relatively innocuous and allows us to study reversible peripheral nerve damage. This model can be developed in other animal species and may be useful to test new therapies for peripheral neuropathy.

Bioavailability of two oral formulations of loratadine 20 mg with concomitant ketoconazole: an open-label, randomized, two-period crossover comparison in healthy Mexican adult volunteers.

BACKGROUND: Loratadine is a long-acting antihistamine with selective peripheral histamine H(1)-receptor antagonistic activity and fewer sedative effects compared with conventional antihistamines, and is widely used in Mexico. Although several generic formulations of loratadine are available in Mexico, based on a literature search, information concerning the bioavailability of each formulation in the Mexican population is not available. OBJECTIVE: The aim of this study was to compare the bioavailability and tolerability of 2 oral formulations of loratadine 20 mg (two 10-mg tablets) used in Mexico: Sensibit (test formulation; Laboratorios Liomont S.A. de C.V., Mexico City, Mexico) and Clarityne (reference formulation; Schering-Plough S.A. de C.V., Mexico City, Mexico) in healthy volunteers. METHODS: This open-label, randomized, 2-period crossover study was conducted at Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, Mexico. Eligible subjects were healthy male Mexican volunteers aged > or=18 years. Subjects were randomly assigned to receive a single 20-mg dose (two 10-mg tablets) of the test or reference formulation, followed by a 2-week washout period, followed by the same dose of the alternate formulation. A 400-mg dose of ketoconazole (2 doses in 24 hours) was administered to each subject before the administration of each formulation, and a 200-mg dose of ketoconazole was given together with each formulation (ie, a total of 600 mg of ketoconazole was administered). Doses were administered after a 12-hour overnight fast. For analysis of pharmacokinetic properties, including C(maX), AUC(0-t), and AUC(0-infinity), blood samples were drawn at 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 5, 8, 12, 16, and 22 hours after dosing. The formulations were considered bioequivalent if the geometric mean ratios of C(maX) and AUC were within the predetermined equivalence range of 80% to 125%. Tolerability was assessed by monitoring vital signs and subject interview regarding the potential presence of adverse events (AEs). RESULTS: Thirty-two subjects were enrolled in the study (mean age, 22 years [range, 18-28 years]; mean weight, 68.9 kg [range, 58-79 kg]; mean height, 170.8 cm [range, 158-183 cm]). Sixteen subjects received the test formulation first. No period or sequence effect was observed. The 90% CIs for the corresponding ratios of CmaX, AUC(0-t), and AUC(0-infinity) were 81.43% to 106.01%, 83.12% to 100.23%, and 84.06% to 101.10% (all, P < 0.05), meeting the predetermined criteria for bioequivalence. Similar results were found for data without a logarithmic transformation. No AEs were reported throughout the study. CONCLUSIONS: In this small study in healthy Mexican volunteers, a single, 20-mg dose of the test formulation of loratadine was found to be bioequivalent to that of the reference formulation based on the rate and extent of absorption when concomitantly administered with ketoconazole. Both formulations were well tolerated.

Bioavailability of two oral formulations of azithromycin 500 mg: a randomized, open-label, two-period crossover comparison in healthy Mexican adult subjects.

BACKGROUND: Azithromycin is related to erythromycin but is more active against gram-negative bacteria and less active against streptococci and staphylococci compared with erythromycin. For these reasons, and because of convenience of dosing (QD for 3 days), azithromycin is widely used in Mexico. Although several generic formulations of azithromycin are available in Mexico, information concerning the bioavailability of each formulation in the Mexican population is not available. OBJECTIVE: The aim of this study was to compare the bioavailability and tolerability of 2 oral formulations of azithromycin 500 mg used in Mexico: Macrozit (trademark of Laboratorios Liomont, S.A. de C.V., Mexico City, Mexico; test formulation) and Azitrocin (trademark of Pfizer, S.A. de C.V., Mexico City, Mexico; reference formulation). METHODS: This 2 x 2, crossover, randomized, open-label study was conducted at the Department of Pharmacology and Toxicology, Universidad Autóma de Nuevo Leon, Monterrey, Mexico. Eligible subjects were healthy volunteers of either sex and with the following characteristics: age > or =19 to 25 years, weight 54 to 77 kg, and height 159 to 177 cm. Subjects were randomly assigned to receive Macrozit followed by Azitrocin, or vice versa, with a 3-week washout period between doses. After a 12-hour (overnight) fast, subjects received a single, 500-mg dose of each formulation. For analysis of pharmacokinetic properties, including C(max), AUC(0-t), and AUC(0-infinity), blood samples were drawn at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 12, 24, 48, 72, 96, and 120 hours after dosing. The formulations were considered bioequivalent if the logarithm (ln)-transformed ratios of C(max) and AUC were within the predetermined equivalence range of 80% to 125% and if P < or = 0.05 for the 90% CIs. Tolerability was assessed by monitoring and subject interview regarding the potential presence of adverse events (AEs). RESULTS: Twenty-eight subjects were enrolled in the study; 27 completed it (14 men, 13 women; mean age, 21.7 years). Fourteen subjects received the test formulation first. No period or sequence effect was observed. The 90% CIs for the corresponding ratios of C(max), AUC(0-t), and AUC(0-infinity) were 80.67 to 107.21, 91.39 to 107.59, and 90.61 to 106.19 (all, P < 0.05). Similar results were found for data without a logarithmic transformation. No AEs were found throughout the study. CONCLUSIONS: In this small study in healthy Mexican volunteers, a single, 500-mg dose of Macrozit was found to be bioequivalent to that of Azitrocin based on the rate and extent of absorption. Both formulations were well tolerated.

Intoxicación de una familia por Karwinskia humboldtiana (tullidora) / Familial intoxication by Karwinskia humboldtiana (tullidora)

La ingestión del fruto maduro de la Karwinskia humboldtiana, arbusto comúnmente conocido como tullidora o coyotillo, provoca una intoxicación descrita en la bibliografía como una parálisis fláccida, simétrica de los miembros inferiores, progresiva y ascendente, que en casos graves puede causar parálisis bulbar y muerte. Se presenta el caso de una familia en la que diez de sus trece miembros ingirieron accidentalmente el fruto de la tullidora; tres fallecieron: el padre y dos hijas. Además, se describe por primera vez, la determinación de las toxinas en sangre por medio de cromatografía en capa fina. Este método resulta útil para el diagnóstico diferencial con otras polirradiculoneuritis, v.gr. poliomielitis y Síndrome de Guillain-Barre

Frecuencia de intoxicación con Karwinskia humboldtiana en México / Frequency of intoxication with Karwinskia humboldtiana in Mexico

La intoxicación con la Karwinskia humboldtiana presenta un cuadro neurológico similar a la poliomielitis, al síndrome de Guillain-Barré y a otras polirradiculoneuritis con las que suele confundirse. El objetivo de este trabajo fue conocer la frecuencia de esta intoxicación, mediante el antecedente de la ingestión del fruto y la detección de toxinas en sangre por cromatografía en capa fina. Se recibieron 154 muestras de casos con parálisis fláccida aguda procedentes de 18 estados de la República. Se corroboró el antecedente de ingestión en 56 de ellos y la detección fue positiva en 50 de los mismos. En 98 pacientes no hubo antecedentes de ingestión y la detección fue negativa en 95 de ellos. Se obtuvo con este método una sensibilidad de 89 por ciento y una especificidad de 96.9 por ciento

Intoxication produced by Karwinskia humboldtiana presents a neurological picture similar to that of poliomyelitis,Guillain-Barre syndrome or other polyradiculoneuritis with which it is frequently confused. The purpose of this paper is to report the frequency of this intoxication, by means of the antecedent of ingestion of the fruit and the detection of toxins in blood using a thin layer chromatography method. One hundred fifty four samples of cases with acute flaccid paralysis from 18 states of the country were received. The antecedent of ingestion in 56 of them was corroborated and the detection was positive in 50 of these. In 98 patients there was not antecedent of ingestion and detection was negative in 95 of them. We estimated that the sensibility and specificity of detection method are 89% and 96.9% respectively.