Pharmacokinetic and pharmacodynamic parameters were established for the enantiomers of the 2-arylpropionic acid (APA) nonsteroidal anti-inflammatory drug (NSAID), ketoprofen (KTP). Each enantiomer was administered separately (1.5 mg/kg) and in a racemic mixture (3 mg/kg) intravenously (i.v.) to a group of eight sheep in a four-way, four-period cross-over study using a tissue cage model of inflammation. Plasma disposition of each KTP enantiomer was similar following separate administration of the pure compounds compared to administration of the racemic mixture. S(+)KTP volume of distribution (Vd(area)) was higher and clearance (ClB) faster than those of R(-)KTP. S(+) and R(-)KTP achieved relatively low concentrations in exudate and transudate. Unidirectional limited chiral inversion of R(-) to S(+)KTP was demonstrated. After R(-)KTP administration S(+)KTP was detected in plasma, but not in either exudate or transudate. Pharmacokinetic/pharmacodynamic (PK/PD) modelling of the data could not be undertaken following R(-)KTP administration because of chiral inversion to S(+)KTP, but the pharmacodynamic parameters, calculated maximum effect (Emax), concentration producing 50% effect (EC50), Hill's coefficient (N), rate constant of elimination of drug effect from the compartment (KeO) and mean equilibration half-life (t1/2KeO) were determined for S(+)KTP after administration of the racemic mixture as well as the pure compound.

Human‐modified habitats rarely yield outcomes that are aligned with conservation ideals. Landscapes that are subdivided by roads are no exception, precipitating negative impacts on populations due to fragmentation, pollution, and road kill. Although many populations in human‐modified habitats show evidence for local adaptation, rarely does environmental change yield outright benefits for populations of conservation interest. Contrary to expectations, we report surprising benefits experienced by amphibian populations breeding and dwelling in proximity to roads. We show that roadside populations of the wood frog, Rana sylvatica, exhibit better locomotor performance and higher measures of traits related to fitness compared with frogs from less disturbed environments located further away from roads. These results contrast previous evidence for maladaptation in roadside populations of wood frogs studied elsewhere. Our results indicate that altered habitats might not be unequivocally detrimental and at times might contribute to metapopulation success. While the frequency of such beneficial outcomes remains unknown, their occurrence underscores the complexity of inferring consequences of environmental change.

Global amphibian decline is due to several factors: habitat loss, anthropization, pollution, emerging diseases, and global warming. Amphibians, with complex life cycles, are particularly susceptible to habitat alterations, and their survival may be impaired in anthropized habitats. Increased mortality is a well-known consequence of anthropization. Life-history theory predicts higher reproductive investment when mortality is increased. In this work, we compared age, body size, and different indicators of reproductive investment, as well as prey availability, in natterjack toads (Epidalea calamita) from agrosystems and adjacent natural pine groves in Southwestern Spain. Mean age was lower in agrosystems than in pine groves, possibly as a consequence of increased mortality due to agrosystem environmental stressors. Remarkably, agrosystem toads were larger despite being younger, suggesting accelerated growth rate. Although we detected no differences in prey availability between habitats, artificial irrigation could shorten aestivation in agrosystems, thus increasing energy trade. Moreover, agrosystem toads exhibited increased indicators of reproductive investment. In the light of life-history theory, agrosystem toads might compensate for lesser reproductive events—due to shorter lives—with a higher reproductive investment in each attempt. Our results show that agrosystems may alter demography, which may have complex consequences on both individual fitness and population stability.

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