Developmental Pharmacology and Age‐Related Phenomena

Abstract

There is a saying: 'Children are not just small adults.' However, and paradoxically, this statement is often followed by a discussion of dosing based on weight, such as in mg kg À1 terms, as in classical pharmacology.Interest in both the young and the old as special populations is now well established, especially in phenomena related to pharmacokinetics. Development of hepatic function and renal processes has received intensive study. Studies of drug responses, and of drug concentrations in body fluids, at different ages are commonplace. This reflects a dramatic change since the early days of clinical pharmacology. However, the study of extreme age groups remains hampered by severe limitations. For example, analytical methods suitable for the small blood samples obtainable from children have required specific development, and ethical problems persist for studies in both the very young and very old age groups.A major problem has been dissociating effects of age itself from effects of age-related practices and phenomena, such as smoking, caffeine, alcohol and other drug consumption, and dietary and exercise habits. Also, age-related disease is an inevitable complication. There remains a great need for longitudinal studies in particular individuals, but the time required for such work is an obvious limitation. Any claim for an agerelated observation must be interpreted in this light. Scientific and regulatory environment in regard to younger and older patientsAwareness that there was a growing need to ensure that drug therapies for the paediatric population were studied with the same level of scientific and clinical rigour as adult therapeutic agents developed slowly between 1968 and 1998. In 1968, children were described by Shirkey as 'therapeutic orphans', but it was not until 1998 that the Food and Drug Administration (FDA) issued its 'Final Rule' on requirements for assessing safety and effectiveness in paediatric patients. Companies had been reluctant to study drugs in children because of the complexity, difficulty and expense of clinical trials in children, preferring to leave dosing recommendations to prescribers, who tended to assume that children merely required relatively low doses in order to respond similarly in the way that adults do. The result was empirical use of medicines without prior evidence-based efficacy and safety studies, with a high incidence of off-label or off-licence use of drugs (i.e. use in ways not approved by the relevant authorities). While often satisfactory for drugs for which there was a long history of experience, the outcome with newer drugs could be beneficial or harmful.Legislative initiatives have catalysed a vast improvement in this situation, such that by 2009, the approved prescribing information on over 100 drugs had been brought up-to-date in regard to paediatric populations as

1-Isobutanoil-2-isopropylisothiourea Phosphate, T1082: A Safe and Effective Prevention of Radiotherapy Complications in Oncology

“…In particular, it may increase the acceptability of such an active substance for i.g. administration, since in this case the processes of absorption from the gastrointestinal tract can prevent the formation of effective tissue concentrations [ 22 ]. In this regard, a comparative study of T1023 and T1082 effects with i.g.…”

“…Already at doses of 1/8 LD 10 (40 mg/kg), the effect of T1023 is usually weak [ 17 , 18 ]. Such features, in our opinion, retain the risks of both the development of negative effects and T1023 ineffectiveness, due to the influence, for example, of metabolic disorders or pathologies that can significantly distort the pharmacokinetics of the active substance [ 22 ]. In this regard, before starting the practical development of T1023, we considered it expedient to search for a more acceptable ‘transport’ form of the active substance among its closest analogues—in the series of 1-isobutanoyl-2-isopropylisothiourea salts with various inorganic and organic acids [ 23 ].…”