Summary
The lure of optimising the effect of the drug on the body (pharmacodynamics) and the body on the drug (pharmacokinetics) has produced an alternative group of products designed to achieve specialised delivery and/or disposition of drugs. A toxic drug may be used in more effective concentrations by targeting the drug to its site of action and decreasing additional systemic toxicity.
Four possible regulatory situations for delivery system and drug have been identified, and generalisations regarding the non-clinical studies needed for the initiation of clinical trials and New Drug Application (NDA) have been described. Problems associated with the identification of appropriate controls have been included, and the importance of basing the choice upon a scientifically rational evaluation of the pharmacodynamic and pharmacokinetic study results emphasised, along with the significance of conducting the non-clinical evaluation using the final formulation.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Bradstreet TE, Clark RL. The statistical evaluation of reproductive toxicity studies. 1987 Annual Meeting of the Biostatistics Subsection, Pharmaceutical Manufacturers’ Association, San Diego, September 27–30, 1987
Cassidy J, Duncan R, Morrison GJ, Strohalm J, Plocova D, et al. Activity of N-(2-hydroxypropyl) methacrylamide copolymers containing daunomycin against a rat tumour model. Biochemical Pharmacology 38: 875–879, 1989
Chen Y, Willmott N, Anderson J, Florence AT. Comparison of albumin and casein microspheres as a carrier for doxorubicin, Journal of Pharmacy and Pharmacology 39: 978–985, 1987
Davis SS, Washington C, West P, Ilium L, Liversidge G, et al. Lipid emulsions as drug delivery systems. Annals of the New York Academy of Sciences 507: 75–88, 1987
Eenink MJD, Maassen GCT, Sam AP, de Nijs H. Development of a new long-acting contraceptive subdermal implant (implanon) releasing 3-keto-desogetrel. Pharmaceutisch Week-blad-Scientific Edition 11 (Suppl.): D7, 1989
Embleton MJ, Habib NA, Garnett MC, Wood C. Unsuitability of monoclonal antibodies to oncogene proteins for anti-tumour drug-targeting. International Journal of Cancer 38: 827, 1986
Fishman PH, Peyman GA, Lesar T. Intravitreal liposome-encap-sulated gentamicin in a rabbit model. Investigative Ophthalmology and Visual Science 27: 1103–1106, 1985
Fujimoto S, Miyazaki M, Endoh F, Takahashi D, Okui K, et al. Mitomycin C carrying microspheres as a novel method of drug delivery. Cancer Drug Delivery 2: 173–181, 1985
Gallo JM, Gupta PK, Hung CT, Perrier DG, Nunedin NA. Evaluation of drug delivery following the administration of magnetic albumin microspheres containing adriamycin to the rat. Journal of Pharmaceutical Sciences 78: 190–194, 1989
Hagiwara A, Takahashi T, Ueda T, Iwamoto A, Torii T. Activated carbon particles as anti-cancer drug carrier into regional lymph nodes. Anti-Cancer Drug Design 1: 313–321, 1987
Kaufman HE. Collagen Shield Symposium. Journal of Cataract and Refractive Surgery 14: 487–488, 1988
Lord P, Allami H, Davis M, Diaz R, Heck P, et al. Minimed Technologis programmable implantable infusion system. Annals of the New York Academy of Sciences 531: 66, 1988
MacLeod DL, Prescott JF. The use of liposomally-entrapped gentamicin in the treatment of bovine staphylococcus aureus mastitis. Canadian Journal of Veterinary Research 52: 445–450, 1988
Manner RH. Therapeutic and protective properties of the corneal collagen shield. Journal of Cataract and Refractive Surgery 14: 496–499, 1988
Mehta RC, Ma JKH. Pharmacokinetics of intrahepatic arterial delivery of microencapsulated mitomycin C. Pharmaceutical Research 5 (Suppl.): S76, 1988
Nacucchio MC, Bellora MJG, Sordelli D, D’Aquino M. Enhanced liposome-mediated antibacterial activity of piperacillin and gentamicin against gram-negative bacilli in vitro. Journal of Microencapsulation 5: 303–309, 1988
Papisov MJ, Savelyev VY, Sergienko VB, Torchilin VP. In vivo kinetics of magnetic drug carriers. Prognostication of biological effect of magnetic drug targeting. Antibiotica et Chemotherapia 33: 744–757, 1988
Phinney RB, Schwartz SD, Lee DA, Mondino BJ. Collagen-shield delivery of gentamicin and vancomycin. Archives of Ophthalmology 106: 1599–1604, 1988
Poland DE, Kaufman HE. Clinical uses of collagen shields. Journal of Cataract and Refractive Surgery 14: 489–491, 1988
Runge MS, Bode C, Matsueda GR, Haber E. Antibody-enhanced thrombolysis: targeting of tissue plasminogen activator in vivo. Proceedings of the National Academy of Science 84: 7659–7662, 1987
Schreier H, Levy M, Mihalko P. Sustained release of liposome-encapsulated gentamicin and fate of phospholipid following intramuscular injection in mice. Journal of Controlled Release 5: 187–192, 1987
Weiner N, Martin F, Riaz M. Liposomes as a drug delivery system. Drug Development and Industrial Pharmacy 15: 1523–1554, 1989
Weissinger J. Nonclinical pharmacologic and toxicologic considerations for evaluating biologic products. Regulatory Toxicology and Pharmacology, in press, 1989
Weissinger J. Pro-active approach to regulation of therapeutic agents: preclinical considerations. Regulatory Affairs 1: 183–190, 1989
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Weissinger, J. Pharmacology and Toxicology of Novel Drug Delivery Systems. Drug-Safety 5 (Suppl 1), 107–113 (1990). https://doi.org/10.2165/00002018-199000051-00017
Published:
Issue Date:
DOI: https://doi.org/10.2165/00002018-199000051-00017