Presence of human papillomavirus in the buccal mucosa of blood donors / Presencia del virus del papiloma humano en la mucosa oral de donantes de sangre

Objective To determine the presence of human papillomavirus (HPV) in the oral mucosa of blood donors (BD) and risk factors associated with HPV and oral cancer. Materials and methods Prospective cross-sectional study, population matched to BD from the National Cancer Institute, Mexico for HPV identification in oral cytological samples using the CLART® Human Papillomavirus 2 Kit (35 genotypes) and risk factors. Results Of 352 BD with signed informed consent, 285 were selected by simple randomization. The prevalence of oral HPV was 17.5% (95% CI 13–21.9%), the genotype was identified in 13 cases, with a total of 16 genotypes (10 high-risk), the most common being 16 and 84. Five cases had multiple infections, three with at least one high-risk type. Associations were found for marital status (OR 3.3) and educational level (OR-1.9). Conclusions The percentage of HPV-positive cases in blood donors with no risk practices was similar to that found in Spanish-speaking population studies in which at least one risk practice was described. The presence of other genotypes with high oncogenic risk and multitype infection, described as a marker of persistence of HPV infection, is highlighted (AU)

Objetivo Identificar la presencia del virus del papiloma humano (VPH) en la mucosa oral de donantes de sangre (DS), así como los factores de riesgo relacionados con el VPH y el cáncer oral. Materiales y métodos Estudio transversal prospectivo. La población correspondió a los DS del Instituto Nacional de Cancerología, México, para la identificación de VPH en muestras citológicas orales con el kit CLART® Human Papillomavirus 2 (35 genotipos) y factores de riesgo. Resultados De 352 DS con firma de consentimiento informado, se seleccionaron 285 por aleatorización simple. La prevalencia de VPH oral fue del 17,5% (IC 95%: 13-21,9%); en 13 casos se identificó el genotipo, con un total de 16 genotipos (10 de alto riesgo), los más frecuentes el 16 y el 84. Cinco casos presentaron infección multitipo, 3 con al menos un tipo de alto riesgo. Las asociaciones encontradas fueron para el estado civil (OR 3,3) y el nivel de estudios (OR 1,9). Conclusiones El porcentaje de casos positivos para VPH en DS sin prácticas de riesgo fue similar a los hallazgos en estudios de población hispanohablante en los que se ha descrito al menos una práctica de riesgo. Se destaca la presencia de otros genotipos con alto riesgo oncogénico y la infección multitipo descrita como marcador de persistencia de la infección por VPH (AU)

Presence of human papillomavirus in the buccal mucosa of blood donors.

OBJECTIVE: To determine the presence of human papillomavirus (HPV) in the oral mucosa of blood donors (BD) and risk factors associated with HPV and oral cancer. MATERIALS AND METHODS: Prospective cross-sectional study, population matched to BD from the National Cancer Institute, Mexico for HPV identification in oral cytological samples using the CLART® Human Papillomavirus 2 Kit (35 genotypes) and risk factors. RESULTS: Of 352 BD with signed informed consent, 285 were selected by simple randomization. The prevalence of oral HPV was 17.5% (95% CI 13-21.9%), the genotype was identified in 13 cases, with a total of 16 genotypes (10 high-risk), the most common being 16 and 84. Five cases had multiple infections, three with at least one high-risk type. Associations were found for marital status (OR 3.3) and educational level (OR-1.9). CONCLUSIONS: The percentage of HPV-positive cases in blood donors with no risk practices was similar to that found in Spanish-speaking population studies in which at least one risk practice was described. The presence of other genotypes with high oncogenic risk and multitype infection, described as a marker of persistence of HPV infection, is highlighted.

Etiology, clinical characteristics, and risk factors associated with severe influenza-like illnesses in Mexican adults.

Objective: The aim of this study was to determine the risk factors associated with severe influenza-like illness (ILI) in Mexican adults that could be useful to clinicians when assessing patients with ILI. Methods: Data from adult patients enrolled from 2010 through 2014 in ILI002 - a prospective hospital-based observational cohort study - were analyzed. Etiology and clinical characteristics were compared between cases of severe ILI (defined as hospitalization and/or death) and cases of non-severe ILI. Results: Overall, 1428 (39.0%) out of a total 3664 cases of ILI were classified as severe. Adjusted analyses showed a higher risk of severe ILI associated with signs and symptoms related to lower tract infection, i.e. cough with sputum (odds ratio (OR) 2.037, 95% confidence interval (CI) 1.206-3.477; P = 0.008), dyspnea (OR 5.044, 95% CI 2.99-8.631; and shortness of breath (OR 5.24, 95% CI 3.0839.124; P < 0.001), and with increases in lactate dehydrogenase (OR 4.426, 95% CI 2.321-8.881; P < 0.001) and C-reactive protein (OR 3.618, 95% CI 2.5955.196; P < 0.001). Further, there was an increased risk of severe ILI with a longer time between symptom onset and inclusion (OR 1.108, 95% CI 1.049-1.172; P < 0.001) and with chronic steroid use (OR 14.324, 95% CI 8.059-26.216; P < 0.001). Conclusions: Respiratory viruses can cause severe ILI. The results of this study highlight the importance of evaluating data compatible with lower tract involvement and previous use of immunosuppressants at baseline, because patients meeting these conditions may develop severe illness.

Immunogenicity and safety of a tetravalent dengue vaccine in dengue-naïve adolescents in Mexico City.

OBJECTIVE: To describe the immunogenicity and safety of a tetravalent dengue vaccine (TAK-003) in healthy adolescents living in Mexico City, an area considered non-endemic for dengue (NCT03341637). METHODS: Participants aged 12-17 years were randomized 3:1 to receive two doses (Month 0 and Month 3) of TAK-003 or placebo. Immunogenicity was assessed by microneutralization assay of dengue neutralizing antibodies at baseline, Months 4 and 9. Solicited and unsolicited adverse events (AEs) were recorded after each vaccination. Serious (SAEs) and medically-attended AEs (MAAEs) were recorded throughout the study. RESULTS: 400 adolescents were enrolled, 391 (97.8%) completed the study. Thirty-six (9%) were baseline seropositive to ≥1 serotypes (reciprocal titer ≥10). Geometric mean titers (GMTs) in baseline seronegative TAK-003 recipients were 328, 1743, 120, and 143 at Month 4, and 135, 741, 46, and 38 at Month 9 against DENV-1, -2, -3, and -4, respectively. Placebo GMTs remained <10. Tetravalent seropositivity rates in vaccine recipients were 99.6% and 85.8% at Months 4 and 9, respectively. One MAAE in each group was considered treatment-related (TAK-003: injection-site erythema, and placebo: pharyngitis). CONCLUSION: TAK-003 was immunogenic against all four serotypes and was well tolerated in dengue-naïve adolescents living in Mexico City.

Immunogenicity and safety of a tetravalent dengue vaccine in dengue-naïve adolescents in Mexico City

[ABSTRACT]. Objective. To describe the immunogenicity and safety of a tetravalent dengue vaccine (TAK-003) in healthy adolescents living in Mexico City, an area considered non-endemic for dengue (NCT03341637). Methods. Participants aged 12–17 years were randomized 3:1 to receive two doses (Month 0 and Month 3) of TAK-003 or placebo. Immunogenicity was assessed by microneutralization assay of dengue neutralizing antibodies at baseline, Months 4 and 9. Solicited and unsolicited adverse events (AEs) were recorded after each vaccination. Serious (SAEs) and medically-attended AEs (MAAEs) were recorded throughout the study. Results. 400 adolescents were enrolled, 391 (97.8%) completed the study. Thirty-six (9%) were baseline seropositive to ≥1 serotypes (reciprocal titer ≥10). Geometric mean titers (GMTs) in baseline seronegative TAK-003 recipients were 328, 1743, 120, and 143 at Month 4, and 135, 741, 46, and 38 at Month 9 against DENV-1, -2, -3, and -4, respectively. Placebo GMTs remained <10. Tetravalent seropositivity rates in vaccine recipients were 99.6% and 85.8% at Months 4 and 9, respectively. One MAAE in each group was considered treatment-related (TAK-003: injection-site erythema, and placebo: pharyngitis). Conclusion. TAK-003 was immunogenic against all four serotypes and was well tolerated in dengue-naïve adolescents living in Mexico City.

[RESUMEN]. Objetivo. Describir la inmunogenicidad y la seguridad de una vacuna tetravalente contra el dengue (TAK-003) en adolescentes sanos residentes en Ciudad de México, considerada un área no endémica de dengue (NCT03341637). Métodos. Se asignó de manera aleatoria a un grupo de participantes de 12 a 17 años en una proporción 3:1 para que recibieran dos dosis (en el mes 0 y en el mes 3) de la vacuna TAK-003 o de un placebo. Se evaluó la inmunogenicidad mediante un análisis de microneutralización de anticuerpos neutralizantes del virus del dengue al inicio del estudio y en los meses 4 y 9. Se registraron los eventos adversos de notificación solicitada y los referidos por iniciativa propia después de cada vacunación. A lo largo del estudio se registraron los eventos adversos graves y los que requirieron atención médica. Resultados. Participaron 400 adolescentes y 391 (97,8%) finalizaron el estudio. 36 adolescentes (9%) fueron seropositivos a ≥1 serotipos (título recíproco ≥10) al inicio del estudio. La media geométrica de los títulos en las personas seronegativas vacunadas con TAK-003 al inicio del estudio fue de 328, 1743, 120 y 143 en el mes 4 y 135, 741, 46 y 38 en el mes 9 en relación con DENV-1, -2, -3 y -4, respectivamente. La media geométrica de los títulos de las personas que recibieron un placebo se mantuvo en <10. Las tasas de seropositividad tetravalente en los vacunados fueron 99,6% y 85,8% a los meses 4 y 9, respectivamente. Se consideró relacionado con el tratamiento un evento adverso con atención médica que tuvo lugar en cada grupo (TAK-003: eritema en el lugar de la inyección; placebo: faringitis). Conclusiones. TAK-003 fue inmunogénica ante los cuatro serotipos y bien tolerada en los adolescentes sin exposición previa al dengue que vivían en Ciudad de México.

[RESUMO]. Objetivo. Descrever a imunogenicidade e a segurança de uma vacina tetravalente contra dengue (TAK-003) em adolescentes saudáveis residentes da Cidade do México, área considerada não endêmica para dengue (ClinicalTrials.gov: NCT03341637). Métodos. Participantes com idade entre 12 e 17 anos foram randomizados a uma proporção de 3:1 para receber duas doses da vacina TAK-003 ou placebo (no mês 0 e no mês 3). A imunogenicidade foi avaliada pelos títulos de anticorpos neutralizantes contra dengue determinados em ensaio de microneutralização ao início do estudo, no mês 4 e no mês 9. A ocorrência de eventos adversos solicitados ou espontâneos foi registrada após cada rodada de vacinação. Eventos adversos graves e eventos adversos que exigiram atendimento médico foram monitorados ao longo de todo o estudo. Resultados. De 400 adolescentes incluídos na amostra estudada, 391 (97,8%) completaram o estudo. Trinta e seis (9%) apresentaram positividade basal a um ou mais sorotipos virais da dengue (título recíproco ≥10). A média geométrica dos títulos de anticorpos nos vacinados com TAK-003 que eram soronegativos ao início do estudo foi de 328, 1743, 120 e 143 no mês 4 e 135, 741, 46 e 38 no mês 9, contra os sorotipos virais DENV-1, DENV-2, DENV-3 e DENV-4, respectivamente. A média geométrica dos títulos de anticorpos no grupo placebo se manteve abaixo de 10. A taxa de soropositividade tetravalente nos vacinados foi de 99,6% no mês 4 e 85,8% no mês 9. Um único evento adverso que exigiu atendimento médico em cada grupo foi considerado relacionado ao tratamento (eritema no local de aplicação no grupo TAK-003 e faringite no grupo placebo). Conclusão. A vacina TAK-003 demonstrou ser imunogênica contra os quatro sorotipos virais da dengue e foi bem tolerada em adolescentes residentes da Cidade do México sem história pregressa de infecção pela dengue.

Underweight, overweight, and obesity as independent risk factors for hospitalization in adults and children from influenza and other respiratory viruses.

BACKGROUND: The relationship between obesity and risk of complications described during the 2009 influenza pandemic is poorly defined for seasonal influenza and other viral causes of influenza-like illness (ILI). METHODS: An observational cohort of hospitalized and outpatient participants with ILI was conducted in six hospitals in Mexico. Nasopharyngeal swabs were tested for influenza and other common respiratory pathogens. RESULTS: A total of 4778 participants were enrolled in this study and had complete data. A total of 2053 (43.0%) had severe ILI. Seven hundred and seventy-eight (16.3%) were positive for influenza, 2636 (55.2%) were positive for other viral respiratory pathogens, and 1364 (28.5%) had no respiratory virus isolated. Adults with influenza were more likely to be hospitalized if they were underweight (OR: 5.20), obese (OR: 3.18), or morbidly obese (OR: 18.40) compared to normal-weight adults. Obese adults with H1N1 had a sixfold increase in odds of hospitalization over H3N2 and B (obese OR: 8.96 vs 1.35, morbidly obese OR: 35.13 vs 5.58, respectively) compared to normal-weight adults. In adults with coronavirus, metapneumovirus, parainfluenza, and rhinovirus, participants that were underweight (OR: 4.07) and morbidly obese (OR: 2.78) were more likely to be hospitalized as compared to normal-weight adults. All-cause influenza-like illness had a similar but less pronounced association between underweight or morbidly obesity and hospitalization. CONCLUSIONS: There is an increased risk of being hospitalized in adult participants that are underweight or morbidly obese, regardless of their viral pathogen status. Having influenza, however, significantly increases the odds of hospitalization in those who are underweight or morbidly obese.

Vitamin D, not iron, is the main nutrient deficiency in pre-school and school-aged children in Mexico City: a cross-sectional study.

INTRODUCTION: In 2012, the Mexican National Health Survey showed a moderate prevalence rate of vitamin D deficiency, around 16%, in a national representative sample of children. A decreasing prevalence of anemia during the last 15 years has been observed in Mexico. The aim of this study was to determine the levels of vitamin D in children 3-8 years old in four different locations within the metropolitan area of Mexico City and to compare them to levels of iron and zinc as references of nutritional status. METHODS: One hundred and seventeen healthy children aged 3-8 years attending four hospitals in Mexico City were invited to participate. All children received medical and nutritional evaluation, and blood samples were obtained. RESULTS: Children were selected in the four hospitals between April and August 2008. More than half (51.3%) were boys; their average age was 5.5 ± 1.6 years. The mean height and weight of the children were 112.1 ± 11.2 cm and 20.2 ± 4.9 kg respectively, with a body mass index [BMI] of 15.8 ± 1.7 kg/m². The mean Z-score (BMI) was 0.007 ± 0.999. The prevalence of subjects with deficient levels of 25-OH-vitamin D (<50 nmol/l) was 24.77%. None of the children had haemoglobin levels below the anaemia threshold, and zinc determination revealed 8.26% of individuals with deficient levels (<65 µg/dL). These data confirm the findings reported in the latest National Nutrition Survey (ENSANUT 2012) about the sustained reduction of anaemia prevalence among preschool and schoolchildren since 1999 and the rising rates of vitamin D deficiency in the same population. Similar to other studies, we found a link between socioeconomic status and the deficiency of micronutrients, these being markers of better nutrition, and vitamin D is remarkably related to the quality of the diet. This finding has not been considered in our population before. CONCLUSIONS: There is evidence of a sustained decrease of anaemia in Mexican children due to general enrichment of foods and focus on vulnerable populations, while vitamin D deficiency seems to have increased. More studies are needed to obtain more information on vitamin D levels at different ages and definition of susceptible groups in order to investigate the possibility of general population measures such as enrichment, which have proven to be effective.

Vitamin D, not iron, is the main nutrient deficiency in pre-school and school-aged children in Mexico City: a cross-sectional study / La vitamina D, y no el hierro, es la principal deficiencia nutricional en niños preescolares y escolares en la ciudad de México: un estudio transversal

Introduction: In 2012, the Mexican National Health Survey (ENSANUT 2012) showed a moderate prevalence rate of vitamin D deficiency, around 16%, in a national representative sample of children. A decreasing prevalence of anemia during the last 15 years has been observed in Mexico. The aim of this study was to determine the levels of vitamin D in children 3-8 years old in four different locations within the metropolitan area of Mexico City and to compare them to levels of iron and zinc as references of nutritional status. Methods: One hundred and seventeen healthy children aged 3-8 years attending four hospitals in Mexico City were invited to participate. All children received medical and nutritional evaluation, and blood samples were obtained. Results: Children were selected in four hospitals between April and August 2008. More than half (51.3%) were boys; their average age was 5.5 ± 1.6 years. The prevalence of subjects with deficient levels of 25-OH-vitamin D (< 50 nmol/L) was 24.77%. None of the children had haemoglobin levels below the anaemia threshold, and zinc determination revealed 8.26% of individuals with deficient levels (< 65 μg/dL). These data confirm the findings reported in ENSANUT about the sustained reduction of anaemia prevalence among preschool and schoolchildren and the rising rates of vitamin D deficiency in the same population. Similar to other studies, we found a link between socioeconomic status and micronutrient deficiency, these being markers of better nutrition, and vitamin D is remarkably related to the quality of the diet. This finding has not been considered in our population before. Conclusions: There is evidence of a sustained decrease of anaemia in Mexican children due to general enrichment of foods and focus on vulnerable populations, while vitamin D deficiency seems to have increased. More studies are needed to obtain more information on vitamin D levels at different ages and definition of susceptible groups in order to investigate the possibility of general population measures such as enrichment, which have proven to be effective (AU)

Introducción: en 2012 la Encuesta Nacional de Salud y Nutrición (ENSANUT) mostró una prevalencia moderada de deficiencia de vitamina D, alrededor del 16%, en una muestra de niños representativa del país. A su vez, la anemia carencial ha disminuido durante los últimos 15 años en México. El objetivo del presente estudio fue determinar los niveles de vitamina D en niños de 3 a 8 años de edad en cuatro diferentes regiones dentro del área metropolitana de la Ciudad de México y compararlos con los niveles de hierro y zinc como referentes del estado nutricional. Métodos: ciento diecisiete niños sanos de 3 a 8 años de edad que regularmente asisten a cuatro diferentes hospitales en la Ciudad de México fueron invitados a participar. Todos los niños recibieron una evaluación médica y nutricional, y se obtuvieron muestras de sangre. Resultados: se reclutaron niños en los cuatro hospitales entre abril y agosto del 2008. Más de la mitad (51,3% fueron niños, su edad promedio fue de 5,5 ± 1,6 años. La prevalencia de sujetos con niveles deficientes de 25-OH-vitamina D (< 50 nmol/l) fue de 24,77%. Ninguno de los niños tuvo niveles de hemoglobina por debajo del umbral de la anemia y la determinación de zinc reveló que 8,26% de los individuos tenían niveles deficientes (< 65 μg/dl). Estos datos confirman los hallazgos reportados en el ENSANUT acerca de la reducción sostenida en la prevalencia de anemia en escolares y preescolares, pero también muestran que se eleva la de deficiencia de vitamina D en esta población. De forma similar a otros estudios, encontramos un vínculo entre el estatus socioeconómico y la deficiencia de micronutrimentos en tanto que estos son marcadores de mejor estado nutricional y la vitamina D se relaciona notablemente con la calidad de la dieta. Estos hallazgos no se han considerado previamente en nuestra población. Conclusiones: existen datos que sugieren una disminución progresiva de la anemia en niños mexicanos debido a una fortificación general de los alimentos y el enfoque en población vulnerable, mientras que la deficiencia de vitamina D parece haber incrementado. Se requieren más estudios para obtener más información acerca de los niveles de vitamina D en distintos grupos de edad y definir a los grupos susceptibles para investigar la posibilidad de llevar a cabo medidas de impacto en la población general como enriquecimiento de alimentos, que ha probado ser efectiva en otros nutrimentos (AU)

Assessment of bivalent and tetravalent dengue vaccine formulations in flavivirus-naïve adults in Mexico.

UNLABELLED: Several ChimeriVax-Dengue (CYD)-based vaccination strategies were investigated as potential alternatives to vaccination with tetravalent CYD vaccine (CYD-TDV) in this phase IIa trial conducted in 2008-9 in 150 healthy adults. Participants were randomized and vaccinated on D0 and D105 (± 15 days). One group received bivalent CYD vaccine against serotypes 1 and 3 (CYD-1;3) on day 0 and CYD-2;4 on day 105 (± 15 days). Two groups received an injection at each timepoint of a tetravalent blend of CYD-1;3;4 and a VERO cell derived, live attenuated vaccine against serotype 2 (VDV-2), or the reference CYD-TDV. A fourth group received Japanese encephalitis (JE) vaccine on days -14, -7 and 0, followed by CYD-TDV on day 105. Viraemia was infrequent in all groups. CYD-4 viraemia was most frequent after tetravalent vaccination, while CYD-3 viraemia was most frequent after the first bivalent vaccination. Immunogenicity as assessed by 50% plaque reduction neutralisation test on D28 was comparable after the first injection of either tetravalent vaccine, and increased after the second injection, particularly with the blended CYD-1;3;4/ VDV-2 vaccine. In the bivalent vaccine group, immune response against serotype 3 was highest and the second injection elicited a low immune response against CYD 2 and 4. Immune responses after the first injection of CYD-TDV in the JE-primed group were in general higher than after the first injection in the other groups. All tested regimens were well tolerated without marked differences between groups. Bivalent vaccination showed no advantage in terms of immunogenicity. CLINICAL TRIAL REGISTRATION NUMBER: NCT00740155.

Bioavailability of two oral formulations of a single dose of levofloxacin 500 mg: an open-label, randomized, two-period crossover comparison in healthy Mexican volunteers.

BACKGROUND: Levofloxacin is a synthetic fluoroquinolone with a broad spectrum of antibacterial activity. It is indicated for the treatment of respiratory, sinus, skin, and urinary tract infections. Although generic formulations of oral levofloxacin are marketed in Mexico, a literature search did not identify published data concerning the bioavailability of these formulations; these data would be relevant to secure marketing of a test formulation in Mexico. OBJECTIVE: The aim of this study was to compare the bioavailability and determine the bioequivalence of a test formulation (an oral tablet containing levofloxacin 500 mg) with its corresponding listed reference-drug formulation in Mexico (a list issued by Mexican Health Authorities). METHODS: A single-dose, open-label, randomized-sequence, 2-period crossover design was used in this study. Eligible participants were healthy Mexican adults of either sex, randomly assigned to receive the test formulation followed by the corresponding reference formulation, or vice versa, with a 1-week washout period between doses. After a 10-hour overnight fast, the participants received the assigned formulation. Plasma concentrations of levofloxacin were determined using high-performance thin-layer chromatography, and densitometric analysis was performed at 300 nm. For the analysis of pharmacokinetic parameters, including C(max), AUC0(-24), and AUC(0-infinity)), blood samples were drawn at baseline and at 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours after administration. The test formulation was considered to meet the criteria for bioequivalence if the geometric mean ratios (test/reference) were with- in the predetermined range of 80% to 125%. Tolerability was determined by clinical assessment, vital signs, laboratory analysis, and interviews with participants about adverse events. RESULTS: A total of 26 participants were enrolled, including 14 men and 12 women with a mean (SD) age of 24 (4) years (range, 18-34 years), weight of 62.2 (10.0) kg (range, 45.5-80.0 kg), height of 163 (9) cm (range, 148-176 cm), and body mass index of 23.3 (2.4) kg/m(2) (range, 19.2-27.1 kg/m(2)). The 90% CIs for log-transformed C(max), AUC(0-24), and AUC(0-infinity) were 94.48% to 106.22%, 90.01% to 116.44%, and 85.11% to 114.00%, respectively. Eleven participants reported a total of 20 adverse events during the study. None of the adverse events were considered serious. CONCLUSIONS: In this small study in healthy, fasting Mexican adults, a single 500-mg dose of the test formulation of orally administered levofloxacin met the regulatory requirements to assume bioequivalence based on the rate and extent of absorption. Both formulations were well tolerated.

Bioavailability of two sublingual formulations of ketorolac tromethamine 30 mg: a randomized, open-label, single-dose, two-period crossover comparison in healthy Mexican adult volunteers.

BACKGROUND: Ketorolac tromethamine (ie, ketorolac) is an NSAID that appears to have several mechanisms of action, including inhibition of prostaglandin synthesis, modulatory effect on opioid receptors, and nitric oxide synthesis. Ketorolac is used in the treatment of pain. There are various generic formulations of sublingual ketorolac available in Mexico. However, a literature search did not identify published data concerning the bioavailability of these formulations in the Mexican population. OBJECTIVE: The aim of this study was to compare the bioavailability of 2 sublingual formulations of ketorolac 30-mg tablets in healthy Mexican adult volunteers. METHODS: This was a randomized-sequence, open-label, single-dose, 2-period crossover (2 dosing periods x 2 treatments) study comparing the bioavailability of two 30-mg sublingual tablet formulations of ketorolac. Healthy Mexican adult (aged, 18-55 years) men and women were eligible for inclusion. Subjects were randomly assigned in a 1:1 ratio to receive a single dose of the test formulation or the reference formulation. After a 12-hour overnight fast, subjects received a single dose of the corresponding formulation. There was a 7-day washout period between administration periods. Plasma samples were obtained over a 24-hour period after administration. Plasma ketorolac concentrations were analyzed by high-performance liquid chromatography for analysis of pharmacokinetic properties, including Cmax, AUC0-24, and AUC0-infinity. Blood samples were drawn immediately after sublingual placement of the drug and at 10, 20, 30, 40, 50, 60, 75, and 90 minutes and 2, 4, 6, 8, 10, 12, and 24 hours after dosing. The formulations were considered bioequivalent if the geometric mean ratios of Cmax and AUC were within the predetermined range of 80% to 125% and if P for the 90% CIs was <0.05. Tolerability was assessed by vital sign monitoring, laboratory analysis results, and subject interviews. RESULTS: A total of 27 subjects (18 women, 9 men; mean [SD] age, 27 [9] years [range, 18-47 years]; weight, 61 [8] kg [48-79 kg]; height, 163 [8] cm [150-180 cm]) were enrolled and completed the study. Fourteen subjects received the test formulation first. No period or sequence effect was observed. The 90% CIs for the corresponding differences in natural log Cmax, AUC0-24, and AUC0-infinity were 95.94% to 114.66%, 98.34% to 105.90%, and 99.25% to 108.36%, respectively (all, (P) < 0.05), meeting the predetermined criteria for bioequivalence. Sixteen subjects experienced a total of 20 adverse events (AEs) during the study. None of the AEs were considered serious. One AE (nausea) appeared to be related to use of the reference formulation. CONCLUSIONS: In this small study in 27 healthy Mexican adult volunteers, the test formulation of a single, 30-mg sublingual tablet of ketorolac appeared to be bioequivalent to the reference formulation based on the rate and extent of absorption. Both formulations were well tolerated.