A review of basic research on immaturity and its influences on the effects and disposition of drugs, together with a consideration of known drug hazards in human infantsIn recent years a series of therapeutic misadventures involving infants has brought forcibly to the forefront the problem of the therapeutic implications of immaturity. That the itnmature organism is not merely a miniature of the mature has, of course, long been recognized, and numerous differences between mature and immature animals or human beings in the response to drugs have been demonstrated. Only recently, however, have we even begun to appreciate the practical importance and complexity of the problem, which will be termed "developmental pharmacology." This term is intended to encompass the problem of the influence of immaturity and the developmental process on the pharmacologic response and, conversely, the effects of drugs upon maturation and development.This problem has been the subject of a Preparation of this review and original work reported herein were supported by a Public Health Service research career program award (5-K3-HD-13,978), a research grant (HD-00615) from the National Institute of Child Health and Human Development, and a grant from Merck & Co., Inc.Received for publication April 17, 1964. 432number of reviews, commentaries, and editorials,80, 92, 114, 144, 208, 214, 215, 249, 277, 316, 339. 343, 355, 358, 374, which have emanated principally from the field of pediatrics and, in the main, have concerned themselves with clinical correlates. It is the purpose of this review to compile and correlate as much of the basic and clinical data as could be found in order, hopefully, to (1) shed further light on the problem, (2) make much scattered information more readily available to those who may be interested in this subject, and (3) focus the attention of people in other diSCiplines upon a problem which has assumed great proportions in pediatriCS. ReViewing past basic work in the field was difficult because relevant papers were included under nearly every conceivable heading in the literature indices, there being no special category for this problem. Often as not, indeXing was on the basis of the specific drug under study. Consequently, no claim of completeness is made and I apologize for, and would appreciate hearing of, any inadvertent omissions. This article will consider only the postnatal effects of drugs and will not discuss the extremely important problem of teratogenic or fetal effects of drugs.
We describe a "highly-performance" liquid chromatographic method in which 8-chlorotheophylline is used as an internal standard to determine acetaminophen and salicylate simultaneously in plasma samples. Therapeutic as well as toxic concentrations can be determined on samples as small as 50 micro L, which makes the method particularly useful for determinations on samples from young children. The procedure requires a simple extraction of the drugs, and the chromatography is completed in 6 min.
SPECIES DIFFERENCES I N I 7-HYDROXYCORTICOSTEROIDS 7injection, the solubilizer used and the handling of the animals, particularly after irradiation, were not involved in either the rate of mortality or the total mortality because if they had been, definite differences in both of these factors would have shown up in the pre-and post-irradiation methylglucamine groups. The non-irradiated control groups and the salinemethylglucamine and flavonoid injected control groups had no deaths during the experimental period or at any time thereafter up to 60 days. This indicates that the deaths obtained in the medicated irradiated groups were not due to the flavonoids themselves. Discussion.The results herein reported concerning the ineffectiveness of parenterally administered rutin, hesperidin, hesperidin methyl chalcone, and naringin in modifying Roentgen ray irradiation mortality in guinea pigs confirm the observations of Dauer and Coon ( 10) who gave rutin, hesperidin methyl chalcone, and citrus vitamin P by the oral route. The results of previous investigators (2,4,7,10) as well as our own would definitely indicate that the flavonoids are incapable of modifying the radiation syndrome in mice, rats, guinea pigs, or dogs. Summary.It has been shown that rutin, hesperidin, hesperidin methylchalcone, and naringin were ineffective in modifying Roent-gen ray irradiation lethality in guinea pigs. There was an indication that post-irradiation medication with rutin may have increased the rate of mortality.
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