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At least 19 recordsLinked to original sources
PubMed1991

The new drug approvals of 1987, 1988, and 1989: trends in drug development.

The new drug approvals of 1987, 1988, and 1989 were analyzed to determine whether there are any emerging trends in the US drug development and review processes. Sixty-four new drugs were approved by the FDA during this period, of which 55 met the Center for the Study of Drug Development's definition of a new chemical entity (NEC). For the 55 NCEs, the mean length of the investigational new drug application (IND) phase (IND filing to NDA submission) was 5.2 years, the new drug application (NDA) phase (NDA submission to approval) was 2.9 years, and the total phase (IND filing to NDA approval) was 8.1 years. Nine of the 55 NCEs were classified by the FDA as 1A (important therapeutic gain), 15 were classified as 1B (modest gain), 29 were classified as 1C (little or no gain), and 2 were classified as 1AA (drugs to treat AIDS and AIDS-related conditions); 10 drugs were granted orphan status. The mean NDA phase for 1A drugs was 2.4 years; 1B drugs, 2.9 years; 1C drugs, 3.1 years; 1AA drugs, 1.4 years; and orphan drugs, 2.5 years. Forty-four of the 55 NCEs (80%) were available in foreign markets before US approval was given, with a mean of 6.5 years of prior marketing. These data are consistent with figures for previous years and suggest little change in the rate of new drug development and review in the United States.

Drugs, Investigational↗
PubMed1987

Trends in drug development: the 1985-86 new drug approvals.

New drug approvals in 1985 and 1986 were analyzed to determine whether any new trends have emerged in the US drug development process. Fifty-three new drugs (including three biologic products) were approved during this period; 46 met the Center for the Study of Drug Development's definition of a new chemical entity (NCE). More than 70% of the 46 approvals were granted in the fourth quarter, 50% in December alone. Four were FDA classified as 1A (important therapeutic gain), 24 as 1B (modest gain), and 16 as 1C (little or no gain); two biologics were not classified. Nine drugs were given orphan status. For the 37 non-orphan drugs, the duration of the "development phase" (IND filing to NDA submission) was 5.6 years; the "review phase" (NDA submission to approval) was 2.6 years; and the "total time" (IND filing to NDA approval) was 8.2 years. Review phase for the four 1A drugs was 2.4 years; for the 24 1B drugs, 2.6 years; for the 16 1C drugs, 2.8 years; and for the nine orphan drugs, 2.7 years. Of the 46 drugs, 33 (71.7%) were available in foreign markets prior to US approval with a mean of 5.5 years of prior marketing. Although the total of 46 NCE approvals in 1985 and 1986 represents a two-year high, there has been a dramatic shift towards fourth quarter approvals. Lengths of the development and FDA review phases are in keeping with those values for previous years.

Humans↗
PubMed1990

The role of ethnopharmacology in drug development.

There are 119 drugs of known structure that are still extracted from higher plants and used globally in allopathic medicine. About 74% of these were discovered by chemists who were attempting to identify the chemical substances in the plants that were responsible for their medical uses by humans. These 119 plant-derived drugs are produced commercially from less than 90 species of higher plants. Since there are at least 250,000 species of higher plants on earth, it is logical to presume that many more useful drugs will be found in the plant kingdom if the search for these entities is carried out in a logical and systematic manner. The first and most important stage in a drug development programme using plants as the starting material should be the collection and analysis of information on the use(s) of the plant(s) by various indigenous cultures. Ethnobotany, ethnomedicine, folk medicine and traditional medicine can provide information that is useful as a 'pre-screen' to select plants for experimental pharmacological studies. Examples are given to illustrate how data from ethnomedicine can be analysed with the aim of selecting a reasonable number of plants to be tested in bioassay systems that are believed to predict the action of these drugs in humans. The ultimate goal of ethnopharmacology should be to identify drugs to alleviate human illness via a thorough analysis of plants alleged to be useful in human cultures throughout the world. Problems and prospects involved in attaining this goal are discussed.

Drug Evaluation, Preclinical↗
PubMed2026

The Computational Revolution in Natural Product Research: A Data-Driven Roadmap for Next-Generation Drug Development.

Natural products (NPs) have historically provided the foundational scaffolds for drug development, yet traditional bioprospecting faces critical limitations: high rediscovery rates, laborious isolation workflows, and substantial attrition during clinical translation. The emergence of big data technologies is fundamentally transforming this landscape, enabling a shift from serendipity-based discovery toward systematic, data-driven approaches. This review examines how the integration of artificial intelligence (AI), machine learning (ML), and multi-omics datasets is accelerating natural product research across three key domains: (1) genome mining for biosynthetic gene cluster identification using platforms such as antiSMASH, (2) cheminformatics-driven prediction of structure-activity relationships and ADMET properties, and (3) metabolomics-guided dereplication to prioritize novel bioactive scaffolds. We evaluate the convergence of genomics, metabolomics, and computational chemistry in enabling in silico lead optimization and the discovery of cryptic metabolites from previously inaccessible microbial taxa. While challenges in data standardization and scalability persist, the synergy between big data and NP research is accelerating clinical translation. Despite persistent challenges in data standardization, scalability, and equitable benefit-sharing, the convergence of big data and NP research is poised to redefine drug development. These advances position computational NP research as a cornerstone of next-generation drug development.

big data analytics↗
PubMed1988

Detection of populations at risk and problem drugs during drug development and in pharmacotherapy.

Rational drug therapy requires knowledge about the ratio of risk (adverse drug reaction) to benefit (therapeutic efficacy) for all drugs to be used in humans. However, with newly marketed drugs, the risk/benefit ratio is usually not sufficiently known. Safety is often less well defined than efficacy. This is the result of the present mode of drug development. Premarketing studies are conducted in comparatively small, homogenous populations over relatively short time intervals and under standardized conditions. Only after marketing are larger, more diversified populations exposed over prolonged times, often under uncontrolled conditions. Adverse drug reactions (ADRs) are the result of either overdosage, or allergic or idiosyncratic reactions. They can be life-threatening or mild. Some of the ADRs are common (greater than 1:10); others are very rare (less than 1:1000). The overall rate of ADR occurrence in ambulatory and hospitalized patients is high enough to have significant socioeconomic consequences. Some of the risk populations can be suspected a priori: elderly, multimorbid patients and patients with compromised drug elimination who may be overdosed if the regimens are not appropriately modified. Some problem drugs may be recognized if they display one or more of the following characteristics: narrow therapeutic index, steep dose-effect relationship, nonlinear kinetics, variable bioavailability, and pharmacogenetically determined kinetics. Other individuals at risk, however, may not be readily identifiable. They develop allergic and idiosyncratic reactions after drug exposure without exhibiting easily recognizable predisposing factors. In order to determine the number of individuals so affected, and the associated drugs as quickly as possible during the developmental process, specific ADR surveillance measures are taken.(ABSTRACT TRUNCATED AT 250 WORDS)

Drug Hypersensitivity↗
PubMed1990

The place of simultaneous pharmacokinetic pharmacodynamic modeling in new drug development: trends and perspectives.

The potential applications in drug development of pharmacokinetic-pharmacodynamic modeling are numerous: optimal medication regimen, design of galenic forms, identification of specific effects of metabolites and enantiomers. Nevertheless, this methodology is presently under-used, as appears from an analysis of the literature. We examine this point as well as progress in both non-invasive pharmacodynamic measurement and specific experimental design that could lead to a future extension of PK-PD in toxicology and phase I drug development.

Drug Evaluation↗
PubMed1992

The decline in new drug development.

The future depends on innovation, not imitation. New drug development can be encouraged in a number of ways (Table 4), and the rewards are great. Who knows what dramatic drug discoveries remain to be found in a new synthetic compound, a fresh soil sample, or a plant obtained from some pristine forest? In any event, let us all hope that the molecular roulette that has governed drug development in the past will be replaced by a more rational, and less empirical, approach.

Chemistry, Pharmaceutical↗
PubMed1975

Biological screening in the U.S. Army antimalarial drug development program.

The methods of testing drugs in the United States Army Antimalarial Drug Development Program are described. To date over two hundred thousand compounds have been screened. For each 3,000 compounds evaluated in the primary screen, only 1 is assessed for efficacy in the final test system. Of those potential antimalarials assessed in this last system, only about half are deemed worthy of preclinical toxicological evaluation.

Animals↗
PubMed1990

Interspecies scaling and comparisons in drug development and toxicokinetics.

1. Methods of interspecies extrapolation using physiological models and allometric scaling have been reviewed with their possible application to drug development, both for candidate drug selection and the interpretation of toxicokinetic data. 2. Physiological models offer a mechanistic approach to extrapolation from one species to another, examining individual components which interrelate to produce the characteristics of the whole system. Tissues of interest are arranged in anatomical order based on blood circulation, and the disposition of a drug can be simulated with knowledge of tissue size (volume), tissue perfusion (blood flow), drug permeability, binding of the drug between the tissue and blood (partition), as well as elimination. Using this approach the behaviour of the drug under different conditions, such as dose route, disease state or animal species, can be predicted. 3. The alternative approach of allometric scaling is an empirical examination of relationships between size, time and its consequences. A regression of the logarithm of the pharmacokinetic parameter and the logarithm of the body weight of the animal species produces a linear relationship which enables the value of pharmacokinetic parameters in any animal species to be calculated from the product of an allometric coefficient and the body weight to a power function. 4. Whilst this technique gives acceptable predictions for the pharmacokinetics of those drugs eliminated renally, or which are blood flow-dependent, there is poor prediction for humans for low clearance drugs primarily eliminated by the mixed-function oxidase system. This appears to be a result of differences in maturation, and can be corrected for by including a brain weight or maximum life-span potential term into the allometric equation. 5. Of the two approaches described for extrapolation of pharmacokinetics between animal species, physiological models tend to be resource-demanding and costly, with more frequent failures, but can be invaluable for examining target organ exposure and for the targeting of drugs as in cancer chemotherapy. For routine drug development, however, allometric scaling is potentially more useful since it uses data which are routinely obtained and the calculations are relatively simple. 6. The problems of intraspecies scaling from high-dose data to low-dose predictions are discussed with respect to current models of dose levels. A new approach is proposed using a modified Hill equation based on drug exposure, which should allow for a more meaningful determination of the toxicity of a compound with different drug exposures.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMedDate not supplied

Human hepatocytes as a key in vitro model to improve preclinical drug development.

Over past decades, numerous in vitro and/or ex vivo models have been developed to investigate drug metabolism. In the order of complexity we found the isolated perfused liver, hepatocytes in co-culture with epithelial cells, hepatocytes in suspension and in primary culture and subcellular hepatic microsomal fractions. Because they can be easily prepared from both animals (pharmacological and toxicological species) and humans (whole livers as well as biopsies obtained during surgery) hepatocytes in primary culture provide the most powerful model to better elucidate drug behavior at an early stage of preclinical development such as: the characterization of main biotransformation reactions, the identification of phase I and phase II isozymes involved in such reactions, the evaluation of inter-species differences allowing the selection of a second toxicological animal species more closely related to man on the basis of metabolic profiles, the detection of the inducing and/or inhibitory effects of a drug on metabolic enzymes, the prediction of drug interactions, the estimation of inter-individual variability in biotransformation reactions. The use of hepatocytes, and in particular those obtained from humans, at an early stage of drug development allows the obtention of more predictive preclinical data and a better knowledge of drug behavior in humans before the first administration of the drug in healthy volunteers.

Animals↗
PubMed1991

Growth factor and oncogene signalling pathways as targets for rational anticancer drug development.

There is a critical need for new targets, in addition to DNA, for anticancer drug development. A recently discovered target is the intracellular signalling pathways that mediate the actions of growth factors and oncogenes on cell proliferation. Two important pathways, the myo-inositol and protein tyrosine kinase signalling pathways are reviewed. Three classes of compounds that modulate myo-inositol signalling are discussed. These are: 1) the D-3-substituted-3-deoxy-myo-inositol analogues that act as antimetabolites of myo-inositol and show selective growth inhibition of some transformed cells; 2) the alkaloid staurosporine that acts as a potent inhibitor of protein kinase C and of platelet-derived growth factor (PDGF) receptor protein tyrosine kinase activity; 3) the ether lipid analogues that block growth factor signalling at several points by acting as inhibitors of protein kinase C, phosphoinositide specific phospholipase C and inositol(1,4,5)trisphosphate-induced Ca2+ release. It is suggested that inhibition of signalling pathways may explain the growth inhibitory effects of these compounds. Other potential signalling target sites for anticancer drug development are discussed.

Alkaloids↗
PubMed1985

The Antiepileptic Drug Development Program: an example of government-industry collaboration.

By collaborating with the pharmaceutical industry in key areas of drug development, the ADD Program of the Epilepsy Branch, National Institute of Neurological and Communicative Disorders and Stroke, has responded to the need for more effective and less toxic antiepileptic drugs than those currently available. The program screens large numbers of compounds for anticonvulsant activity, conducts toxicology studies, and sponsors clinical trials of promising new drugs for the treatment of epilepsy. This collaboration with the pharmaceutical industry is providing a valuable model for a shared drug development program.

Anticonvulsants↗
PubMed1977

Animal models in drug development: historical aspects.

The historical aspects of drug development and evaluation are anecdotically related. Clinical trials have proven the effectiveness of animal tests in the vast majority of cases, and the effort has been well spent. Similar of more noteworthy success may be obtainable with model systems in the study of prostatic cancer.

Animals↗