Estimating the starting dose for entry into humans: Principles and practice

European Journal of Clinical Pharmacology

Volumn 57, Issue 12, 2002, Pages 835-845

  Reigner, Bruno G ^a   Blesch, Karen ^b  

^a F HOFFMANN LA ROCHE LTD   (Switzerland)

^b HOFFMANN LA ROCHE INC   (United States)

Author keywords

Entry into human study; Pharmacokinetics; Starting dose

Indexed keywords

CYTOTOXIC AGENT;

CYTOTOXICITY; DOSE CALCULATION; DRUG EFFECT; DRUG EXPOSURE; DRUG MANUFACTURE; DRUG MECHANISM; DRUG SAFETY; HEALTH SURVEY; INTERMETHOD COMPARISON; MATHEMATICAL ANALYSIS; MEDICAL PRACTICE; METHODOLOGY; ONCOLOGY; PRIORITY JOURNAL; REVIEW;

ANIMALS; ANTINEOPLASTIC AGENTS; DRUG INDUSTRY; HUMANS; MAXIMUM TOLERATED DOSE; NO-OBSERVED-ADVERSE-EFFECT LEVEL; PHARMACEUTICAL PREPARATIONS; PHARMACOKINETICS;

EID: 0035723305     PISSN: 00316970     EISSN: None     Source Type: Journal    
DOI: 10.1007/s00228-001-0405-6     Document Type: Review

References (49)

1. Initial human trials with an investigational new drug (phase 1 and 2): Planning and management
2. Controversy V: Phase I, first-time-in-man studies
3. First-time-in-human dose selection: Allometric thoughts and perspectives
4. The conduct of initial drug studies in man
5. For the first time in man
6. New drugs: First time in man
7. Statistical and ethical issues in the design and conduct of phase I and II clinical trials of new anticancer agents
8. Early cancer clinical trials: Safety, numbers and consent
9. Procedures for preclinical toxicologic evaluation of cancer chemotherapeutic agents: Protocols of the laboratory of toxicology
10. Developmental toxicology
11. Quantitative comparison of toxicity of anticancer agents in mouse, rat, hamster, dog, monkey and man
12. Quantitative relationships between toxic doses of antitumor chemotherapeutic agents in animals and man
13. Quantitative prediction of drug toxicity in humans from toxicology in small and large animals
14. Mouse and large animal toxicology studies of twelve antitumor agents: Relevance to starting dose for phase I clinical trials
15. Animal toxicology for early clinical trials with anticancer agents
16. Choice of starting dose and escalation for phase I studies of antitumor agents
17. Potential roles for preclinical pharmacology in phase I clinical trials
18. Pharmacologically guided phase I clinical trials based upon preclinical drug development
19. The impact of pharmacokinetically guided dose escalation strategies in phase I clinical trials: Critical evaluation and recommendations for future studies
20. Pharmacokinetically guided dose escalation in phase clinical trials. Commentary and proposed guidelines
21. Anticancer drugs
22. Design and results of phase I cancer clinical trials: Three year experience at M.D. Anderson Cancer Center
23. Critique of prospective allometric scaling: Does the emperor have clothes?
24. Clinical pharmacokinetics
25. Some pharmacological consequences of species variation in rates of metabolism
26. Prediction of hepatic metabolic clearance based on interspecies allometric scaling techniques and in vitro-in vivo correlations
27. Allometric issues in drug development
28. The pharmacokinetic principles behind scaling from preclinical results to phase I protocols
29. First time in human for GV196771: Interspecies scaling applied on dose selection
30. In vivo and in vitro kinetics of mofarotene in mouse, rat, dog and man
31. Integration of animal pharmacokinetic and pharmacodynamic data in drug safety assessment
32. Animal pharmacokinetics and interspecies scaling of Ro 25-6833 and related (lactamylvinyl) cephalosporins
33. Use of interspecies scaling in toxicokinetics
34. Pentachlorophenol carcinogenicity: Extrapolation of risk from mice to humans
35. Drug research: From the idea to the product
36. Study design and assessment of wanted and unwanted drug e1ects in phase I/II trials
37. Design of first administration studies in healthy man
38. An evaluation of the integration of pharmacokinetic and pharmacodynamic principles in clinical drug development
39. Genetics
40. Dosing schedule
41. Physiologically based pharmacokinetics of cyclosporine A: Extension to tissue distribution kinetics in rats and scale-up to human
42. Prediction of interindividual variation in drug plasma levels in vivo from individual enzyme kinetic data and physiologically based pharmacokinetic modeling
43. Prediction of hepatic metabolic clearance in man-comparison and assessment of prediction models
44. A quantitative assessment of empirical vs. physiologically based approaches to predict hepatic clearance in man
45. Incorporation of in vitro (hepatocyte) clearances into physiologically-based pharmacokinetic models: Application to extensively metabolized compounds
46. Prediction of human pharmacokinetics based on in vitro and in vivo preclinical data
47. Computer-Assisted Drug Development (CADD): An emerging technology for designing first-time-in man and proof-of-concept studies from preclinical experiments
48. Optimizing the science of drug development: Opportunities for better candidate selection and accelerated evaluation in humans