A Comparative Study of PBPK Model and Allometric Growth Model of Azithromycin in Extrapolation of Adult Pharmacokinetic Data to Pediatric Population / 中国药学杂志

OBJECTIVE: To establish an adult-pediatric transformation model of azithromycin to provide guiding recommendations for clinical using of pediatrics, reduce the risk of medicationfor children, and achieve clinical personalized medication for children. METHODS: The relevant literature was reviewed. The physiological parameters of the azithromycin oral administration test in adults combined with the drug-specific parameters of azithromycin were used to establish an allometric growth model, PBPK model. According to the clinical data of oral azithromycin extracted from individual children, the correctness of the parameter scaling formulas of these two models was verified. These two models were further used to simulate the pharmacokinetic parameters of children and calculate the relative deviation and relative standard error of these parameters. RESULTS: Through simulation, it is found that the pharmacokinetic parameters cmax, tmax, AUC0-∞ obtained by the two models are close to the measured values, which are all within the scope of the literature. It can be considered that the parameter conversion formulas of the two models are correct. Further, the relative deviation and relative standard error of the parameters are calculated, and the relative deviation and relative standard error of the adult-pediatric PBPK prediction model are smaller than those of the allometric growth model. CONCLUSION: The azithromycin PBPK model predicts that children's pharmacokinetic parameters are better than the allometric growth model. The scaling formula for the specific parameters of the oral-dose adult-child model used in this article, which was successfully verified by azithromycin, can be extrapolated to other drugs to facilitate the conversion of other oral-adulterated adult-pediatric models.

Weight-length relationships of six shrimp species caught off the Madeira Archipelago, Northeastern Atlantic / Relações peso-comprimento de seis espécies de camarão capturados ao largo do arquipélago da Madeira, Atlântico Nordeste

Abstract Length and weight relationships and descriptive statistics are reported for six shrimp species caught off the Madeira archipelago between 1983 and 2014 using bottom and floating traps from depths ranging from 50 to 1,300 m. The parameter b ranged between 2.36 for Plesionika ensis and 2.97 for Plesionika williamsi. All species showed a pattern of negative allometric growth. To the authors' knowledge all weight-length relationships presented herein are recorded for the first time from the Madeira area, and in the cases of Ligur ensiferus and Plesionika ensis are the first references worldwide.

Resumo As relações peso-comprimento e a estatística descritiva foram estimadas para seis espécies de camarões, capturados ao largo do arquipélago da Madeira, entre 1983 e 2014, usando armadilhas de fundo e alvoradas entre os 50 e 1.300 metros de profundidade. O parâmetro b variou entre 2,36 para Plesionika ensis e 2,97 para Plesionika williamsi. Todas as espécies evidenciaram um padrão de crescimento alométrico negativo. De acordo com o conhecimento dos autores, todas as relações peso-comprimento são aqui apresentadas pela primeira vez para a área da Madeira e no caso de Ligur ensiferus e Plesionika ensis são a primeira referência mundial.

Weight-length relationships of six shrimp species caught off the Madeira Archipelago, Northeastern Atlantic

Abstract Length and weight relationships and descriptive statistics are reported for six shrimp species caught off the Madeira archipelago between 1983 and 2014 using bottom and floating traps from depths ranging from 50 to 1,300 m. The parameter b ranged between 2.36 for Plesionika ensis and 2.97 for Plesionika williamsi. All species showed a pattern of negative allometric growth. To the authors knowledge all weight-length relationships presented herein are recorded for the first time from the Madeira area, and in the cases of Ligur ensiferus and Plesionika ensis are the first references worldwide.

Resumo As relações peso-comprimento e a estatística descritiva foram estimadas para seis espécies de camarões, capturados ao largo do arquipélago da Madeira, entre 1983 e 2014, usando armadilhas de fundo e alvoradas entre os 50 e 1.300 metros de profundidade. O parâmetro b variou entre 2,36 para Plesionika ensis e 2,97 para Plesionika williamsi. Todas as espécies evidenciaram um padrão de crescimento alométrico negativo. De acordo com o conhecimento dos autores, todas as relações peso-comprimento são aqui apresentadas pela primeira vez para a área da Madeira e no caso de Ligur ensiferus e Plesionika ensis são a primeira referência mundial.

Characterization of the early development of Pseudoplatystoma reticulatum Eigenmann & Eigenmann, 1889 (Siluriformes: Pimelodidae) from the Paraguay River Basin

This study described the initial development of Pseudoplatystoma reticulatum, as well as changes in growth patterns. Morphometric and meristic variables were analyzed during embryonic, larval and juvenile periods, even as allometric growth coefficients for larvae and juveniles. Eggs showed an average diameter of 1.79 mm and broad perivitelline space (23.41%). The total length (TL) of the larvae ranged from 3.05 to 25.72 mm, and the total number of myomeres ranged from 45 to 50 (preanal = 13-16 and postanal = 30-35). Initial pigmentation is poor, concentrated at the extremities of the yolk sac. In the flexion stage, the pigmentation intensifies and forms a longitudinal stripe extending from the snout to the operculum and two longitudinal stripes on the body, one dorsal and the other ventral, that unite at the caudal peduncle. At first, there is a differential growth of the head and tail, and then there is the growth of the body, which shows changes in the ontogenetic priorities of feeding, swimming, and breathing capacities. Our results are very important for ecology, systematics, and hatchering, especially in terms of ontogenetic variation in morphology, growth, feeding, behavior, and mortality of P. reticulatum.

Este estudo descreveu o desenvolvimento inicial de Pseudoplatystoma reticulatum, bem como as mudanças nos padrões de crescimento, testando a hipótese da ocorrência de crescimento diferencial durante a ontogenia inicial da espécie. Variáveis morfométricas e merísticas foram analisadas durante os períodos embrionário, larval e juvenil, assim como os coeficientes de crescimento alométrico para larvas e juvenis. Os ovos apresentaram diâmetro médio de 1,79 mm e espaço perivitelino amplo (23,41%). O comprimento total (CT) das larvas variou de 3,05 a 125,72 mm e o número total de miômeros de 45 a 50 (pré-anal=13-16 e pós-anal=30-35). A pigmentação inicial é escassa, concentrada nas extremidades do saco vitelino. A partir do estágio de flexão a pigmentação se intensifica, formando uma faixa longitudinal que se estende do focinho ao opérculo e duas no corpo, uma dorsal e outra ventral, que se unem no pedúnculo caudal. Inicialmente há um crescimento diferenciado da cabeça e da cauda, com posterior crescimento do tronco, que demonstra mudanças nas prioridades ontogenéticas para as capacidades de alimentação, natação e respiração. Nossos resultados são de grande importância para a ecologia, sistemática e larvicultura, especialmente em termos de variação ontogenética na morfologia, crescimento, alimentação, comportamento e mortalidade P. reticulatum.

Length-weight relationship and condition factor of Aorichthys aor (Hamilton-Buchanan) in Lower Reaches of River Brahmaputra.

The studies were conducted during 2008–2010 to evaluate length-weight relationship and condition factor of Aorichthys aor in lower reaches of River Brahmaputra. 750 nos of fishes having weight of 20g to 1250 g and total length of 10 cm to 55 cm were recorded. The Cube law or Length–weight relationship was calculated as W = 0.00352 L3.246. The coefficient of correlation (r) between observed length & weight and calculated length & weight was 0.96 and 0.93 respectively, which indicated highly significant relationship between length and weight. The exponent (b) value obtained indicating the positive allometric growth pattern. The relative condition factor (Kn) value was found higher in fishes of above 650 g weight groups.

Growth rate studies of marine ornamental fish Pomacentrus caeruleus in artificial conditions.

Aquaculture industry depends on development and testing of protocols for rearing and breeding of new aquaculture species as these techniques vary with species. In the present study attempts have been made to study the effect of temperature and salinity on the rate of growth of the marine ornamental fish, Pomacentrus caeruleus under artificial conditions. Results reveal the length and weight of the fish to increase gradually at an average rate of 0.10 cm and 0.23 g with decreasing salinity (25ppt to 5ppt) at 25ºC and 6.54 condition factor (K). Statistical output indicates a significant positive relationship between K at 25ºC and K at 30ºC (R=0.557, P<0.05). Correlation indicated growth rate to be higher between 25ºC and 30ºC. This is in contrast to the hypothesis which states the weight of the fish to be different at different temperatures, F (2,54)=5.713, P<0.05. Tukey’s test results indicate a significant difference in the weight of the fishes acclimatized at different temperatures. Mortality rate was highest in 20ºC followed by 30ºC while least in 25ºC. The incidence of diseases was highest in 20ºC and the acclimatization period highest in 30ºC. In conclusion it appears that Pomacentrus caeruleus exhibits allometric growth at lower salinities and at a controlled temperature of 25ºC.

Can weight/length relationship predict size at first maturity? A case study with two species of Characidae

A weight/length relationship was established for Astyanax jacuhiensis (Cope, 1894) (n = 370) and Cheirodon ibicuhiensis Eigenmann, 1915 (n = 701), from samples taken monthly in Fortaleza Lagoon, Cidreira, Rio Grande do Sul, from December 1991 through November 1992. Both species showed a polyphasic allometric growth pattern, each stanza described by an independent power equation controlled by a switch function. For C. ibicuhiensis, this change in the growth pattern occurred at 2.948 cm standard length (SL), close to published sizes for the attainment of female maturity. The change in the growth pattern of A. jacuhiensis (SL = 3.481 cm) was below the predicted size at first maturity, and merits further investigation. Although not conclusive, our data suggest that a complex growth pattern is frequent in nature, and perhaps is not usually identified because trends are obscured by natural variability. Despite the increased complexity resulting from the application of a more-complex equation, the identification of a change in the growth pattern could indicate important aspects of fish biology, including the attainment of sexual maturity.

A relação peso/comprimento para Astyanax jacuhiensis (Cope, 1894) (n = 370) e Cheirodon ibicuhiensis Eigenmann, 1915 (n = 701) foi estimada a partir de amostras mensais efetuadas na lagoa Fortaleza, Cidreira, Rio Grande do Sul (dezembro de 1991 a novembro de 1992). As espécies analisadas apresentaram padrão de crescimento alométrico polifásico, sendo cada fase descrita por uma equação potência independente controlada por uma função interruptora. Para C. ibicuhiensis foi identificada uma modificação no padrão de crescimento com 2,948 cm de comprimento padrão (CP), valor próximo à dados publicados relativos ao início da maturação sexual. A alteração observada no padrão de crescimento de A. jacuhiensis (CP = 3,481 cm) encontra-se abaixo do tamanho previsto para a primeira maturação e sugere a necessidade de investigação adicional. Embora não conclusivos, nossos dados sugerem que padrões complexos de crescimento são frequentes na natureza e, talvez, não identificados porque tendências sutis acabam por ser obscurecidas pela variabilidade natural dos dados. Apesar do aumento de complexidade resultante da aplicação de uma equação complexa, a identificação de mudanças no padrão de crescimento pode apontar para aspectos relevantes da biologia de peixes, incluindo a maturação sexual.

Efeito da restrição alimentar pré e pós-natal sobre o crescimento dos órgãos internos de cordeiros Santa Inês / Effects of pre and postnatal nutritional restriction on visceral mass growth of Santa Ines lambs

Avaliaram-se os efeitos da restrição alimentar pré e pós-natal sobre o crescimento dos órgãos internos de cordeiros Santa Inês. Foram utilizados 68 cordeiros distribuídos em três tratamentos: restrição pré-natal (RPRE), restrição pós-natal (RPOS) e sem restrição (controle). Os animais foram abatidos ao nascimento e aos 10, 15, 25, 35 e 45kg de peso vivo. Após o abate, coração, pulmões, traquéia/esôfago, fígado, baço, pâncreas, rúmen/retículo, abomaso, omaso, intestino delgado e grosso foram retirados e pesados separadamente. A análise dos pesos dos órgãos internos dos animais abatidos ao nascimento demonstrou que a restrição pré-natal diminuiu os pesos do coração, pulmões, traquéia/esôfago, abomaso, pancrêas e baço, com médias de 54g, 16g, 22g, 16g, 2g e 5g, respectivamente. Aos 15kg, o peso dos órgãos dos animais submetidos à restrição pré-natal não diferiu dos demais, indicando crescimento compensatório desses órgãos já na fase de aleitamento. Não houve efeito da restrição sobre o peso médio dos órgãos da cavidade torácica, e na cavidade abdominal o rúmen, o intestino delgado e o fígado tiveram seus pesos reduzidos, com médias de 385g, 488g e 371g, respectivamente. Pulmões, traquéia e coração apresentaram crescimento heteregônico negativo (b<1); para a traquéia e o coração dos animais RPRE o comportamento foi isogônico (b=1). O rúmen e o omaso apresentaram crescimento heterogônico positivo (b>1), o abomaso heterogônico negativo (b<1), e os intestinos, o baço e o fígado, isogônico (b=1). O pâncreas dos animais controle e RPOS apresentou crescimento isogônico (b=1), e o dos RPRE heterogônico positivo (b>1). A restrição alimentar pré e pós-natal afetou o tamanho, as taxas de crescimento e o tipo de desenvolvimento de vários órgãos internos de cordeiros Santa Inês, evidenciando a necessidade de suplementação adequada para as fêmeas no terço final da gestação e para os cordeiros, durante a fase de crescimento.

The effects of pre and postnatal nutritional restriction on allometric growth of thoracic and abdominal organs of Santa Inês lambs were evaluated. Sixty-eight lambs were divided into three groups: lambs with prenatal nutritional restriction (PRER), lambs with postnatal nutritional restriction (POSR), and lambs without restriction (control). The lambs in each group were slaughted at birth, 10kg, 15kg, 25kg, 35kg, and 45kg of live weight. After slaughtering, heart, lungs, trachea and esophagus, liver, spleen, pancreas, rumen-reticulum, abomasum, omasum, and small and large intestines were individually weighted. At birth, PRER affected the weights of heart, lungs, trachea and esophagus, abomasum, pancreas, and spleen, with means of 54g, 16g, 22g, 16g, 2g, and 5g, respectively. However, the organs of the PRER lambs at 15kg of live weight showed the same weight of that organs of the others animals, indicating a compensatory growth. POSR did not affect the weight of the organs of thoracic cavity;however, in abdomen cavity, rumen, small intestine, and liver were affected, with means of 385g, 488g, and 371g, respectively. The allometric study showed that rumen and omasum presented a positive heterogonic development; while abomasum presented a negative heterogonic development; and liver, small and large intestines showed an isogonic development. The pancreas of control and POSR lambs presented an isogonic development, while pancreas of PRER lambs showed a positive heterogonic delevopment. In this experiment, the alimentary restriction affected weigth, growth, and type of development of internal organs of Santa Inês lambs, evidencing the importance of the feeding for ewes at the last third of gestation as well as for the lambs during the growth phase.

Crecimiento y reproducción del camarón Atya margaritacea (Decapoda: Atyidae) en el Río Presidio, Sinaloa, México

Growth and reproduction of the shrimp Atya margaritacea (Decapoda: Atyidae) in Río Presidio, Sinaloa, Mexico. Some growth and reproduction parameters of the population of the shrimp Atya margaritacea in Presidio River (Sinaloa, NW Mexico) were studied using 542 organisms collected with a Surber net in five sampling locations distributed from mid- to low river. Total lengths and gross weights ranged from 15 to 96 mm and 0.1 to 25.2 g. The male:female ratio was 1.96:1 and males had larger sizes and weights. The relations of total length (Lt) to gross weight (Pt) were Pt = 1.02x10-5 (Lt)3.2089 for males and Pt = 2.29x10-5 (Lt)3.0159 for females. Growth in males was positively allometric whereas in females it was isometric. The regressions between total lengths and cephalothorax (Lc) were Log Lc = 1.1118 (Log Lt)- 0.6087 for males and Log Lc = 0.9945 (Log Lt)- 0.4321 for females. The relative growth between these body parts was allometrically positive in males and isometric in females; this result indicates a clear sexual dimorphism. Ovigerous females appeared in the rainy season (July to November). The absolute fecundity ranged from 1 860 to 22 400 eggs in females of 43 to 59 mm in length and 1.9 to 6.0 g in weight. The equations relating the number of eggs to length and weight were Fec = 8.3x10-7 (Lt)5.8053 and Fec = 732 (Pt)1.836 respectively. Rev. Biol. Trop. 56 (2): 513-522. Epub 2008 June 30.

Se estudiaron el crecimiento y reproducción de de Atya margaritacea, con base en 542 organismos capturados en cinco sitios distribuidos desde la parte media de la cuenca hasta la desembocadura del río Presidio (Sinaloa, NW de México). La recolecta se realizó mediante el empleo de una red Surber, recolectándose organismos cuya longitud total y peso total variaron de 15 a 96 mm y 0.1 a 25.2 g respectivamente. La proporción macho:hembra fue 1.96:1 y los machos alcanzaron las mayores tallas y pesos. La relación entre la longitud total (Lt) y el peso total (Pt) se estableció mediante el modelo Pt = 1.02x10-5 (Lt)3.2089 para los machos y por Pt = 2.29x10-5 (Lt)3.0159 para las hembras. El crecimiento en machos resultó alométricamente positivo mientras que en hembras fue isométrico. La regresión entre la longitud total y longitud cefalotórax (Lc) fue Log Lc = 1.1118 (Log Lt)- 0.6087 en machos y Log Lc = 0.9945 (Log Lt)- 0.4321 en hembras. El crecimiento relativo entre estas partes del cuerpo resultó alométrico positivo en machos e isométrico en hembras, indicando un claro dimorfismo sexual de estos organismos. Hembras ovígeras se presentaron en la época de lluvias (julio a noviembre). La fecundidad absoluta varió de 1 860 a 22 400 huevos en hembras de 43 y 59 mm de longitud y de 1.9 a 6.0 g de peso. La ecuación que relacionó el número de huevos con la longitud y peso, fue Fec = 8.3x10-7 (Lt)5.8053 y Fec = 732 (Pt)1.836 respectivamente.

Efeito da restrição pré e pós-natal sobre o crescimento dos depósitos de gordura de cordeiros Santa Inês / Effects of pre and postnatal nutritional restriction on internal fats growth of Santa Ines lambs

Avaliaram-se os efeitos da restrição pré e pós-natal sobre o tamanho e o crescimento dos depósitos de gordura de cordeiros Santa Inês. Foram utilizados 68 cordeiros, distribuídos em três tratamentos: com restrição pré-natal (RPRE), com restrição pós-natal (RPOS) e sem restrição (controle). Dentro de cada tratamento, os animais foram aleatoriamente sorteados para serem abatidos após o nascimento e com 10, 15, 25, 35 e 45kg de peso vivo. Os depósitos de gordura (omental, mesentérica, perirenal, pélvica e inguinal) foram registrados. Ao nascimento, os depósitos de gordura foram menores nos animais do tratamento RPRE. Entre 15 a 35kg de peso, a quantidade de gordura foi igual nos animais dos três tratamentos e, a partir desse peso (35kg), com exceção da gordura pélvica, os depósitos no animais do tratamento RPRE foram significativamente maiores. A restrição pré-natal elevou consideravelmente as taxas de ganho da gordura omental, mesentérica, perirenal e pélvica, enquanto a restrição pós-natal influenciou somente a taxa de ganho da gordura inguinal. Cordeiros de todos os grupos apresentaram taxas de desenvolvimento tardias (b>1).

Effects of pre and postnatal nutritional restriction on allometric growth of internal fat deposits in Santa Ines lambs were evaluated Sixty eight lambs were randomly alloted to three different nutritional restriction:prenatal nutritional restriction (PRER), postnatal nutritional restriction (POSR), and a control group without nutritional restriction. Lambs of each group were randomly sampled and slaughtered at birth and weighing 10, 15, 25, 35 and 45kg. Fat depositts (omental, mesenteric, perirenal, pelvic and inguinal) of slaughtered lambs were recorded. At birth fat deposits were small for animals from treatment RPRE. From 15 to 35kg of live weight the amount of fat was similar for animals from all groups but lambs from PRER group, with live body weight heavier than 35kg, showed higher fat deposits except for pelvic fat. Prenatal nutritional restriction increased increased the omental, mesenteric, perirenal, and pelvic fat deposits and postnatal restriction decreased the inguinal fat deposits. Lambs from all groups showed a positive heterogenic development (b>1).