Clinical test

In 1962, amendments to the U.S. Federal Food, Dmg and Cosmetic Act (Kefauver-Harris amendments) promulgated regulations concerning the requirements for premarketing approval by the FDA. This legislation estabUshed requirements of proof of both safety and therapeutic efficacy and strict control of human clinical testing, for example, which have extended the time and cost to market a new dmg. Thus, whereas approximately 40 new dmgs were marketed annually from 1948 to 1962, this number had fallen to 12 by 1966. 

Quahty control during manufacture and of the final product assures batch-to-batch consistency and reflabiUty. Bioavadabihty is checked in early batches produced for clinical testing. Other tests include uniformity of weight and contents, hardness (qv), disintegration rate, dissolution rate, and friabihty. 

Table 1. Clinical Tests Offered on Automated Analyzers ...

One of the serious defects of the conventional amalgams is the corrosion of the Sn Hg phase, which is normally absent or, if it forms, mostiy disappears in amalgams with the increased copper content hence, the term non-y2 amalgams. The phases present in two conventional amalgams used in clinical testing (56,58,62) are... 

Dentifrices are also vehicles for agents that alleviate dentinal hypersensitivity. Among the materials that have given positive results in clinical tests are potassium nitrate [7757-79-1] (5%) and strontium chloride [10476-85-4] (10%). 

An antimicrobial agent that reduces dental plaque and can be deUvered effectively from toothpaste is a combination of Triclosan [3380-34-5] (0.2% in the toothpaste) and zinc citrate (0.5%) (7). This agent influenced plaque accumulation and reduced the incidence of gingival bleeding in clinical tests. Additional dentifrices for improved gingival health are in the offing. 

FIGURE 8.17 Attrition of molecules as they are taken through the clinical testing procedure. It can be seen that very few become drugs (1.34%). Redrawn from [16]. 

Figure 3.117 (a) JM-216, a platinum(IV) compound under clinical tests as an orally administered anti-tumour agent (b) the platinum(II) product of in vivo reduction, likely to be the active... 

In addition to the AT-dependent agents discussed above, various direct Xa inhibitors (e.g., tick anticoagulant peptide, antistatin, DX-9065a) are undergoing clinical testing. Unlike fondaparinux, these drugs also inhibit surface-bound Xa within prothrombinase. 

In breast cancer patients, total PR status is measured for hormonal treatment. The presence of PR is associated with increased survival rates and hormonal responsiveness of mammary tumors. PR agonists are widely used in contraception, HRT, breast cancer, and endometrial hyperplasia. Antiprogestins such as RU486 are used for blocking ovulation and preventing implantation, and in addition they are in clinical testing for the induction of labor and to control various neoplastic transformations. 

The nature of electrochemical instruments makes them very attractive for decentralized testing. For example, compact, battery-operated voltammetric analyzers, developed for on-site measurements of metals (9,10), readily address the growing needs for field-based environmental studies. Similarly, portable (hand-held) instruments are being designed for decentralized clinical testing (11). 

Overview of the non-clinical testing strategy Pharmacology Pharmacokinetics Toxicology... 

Chitosan has been associated with other biopolymers and with synthetic polymer dispersions to produce wound dressings. Biosynthetic wound dressings composed of a spongy sheet of chitosan and collagen, laminated with a gentamicyn sulphate-impregnated polyurethane membrane, have been produced and clinically tested with good results. 

Naltrexone in combination with lactide/glycolide copolymer has been investigated (83-87). Chiang (85) reported the clinical evaluations of a bead preparation containing 70% naltrexone and 30% of a 90 10 lactide/glycolide copolymer. Each subject received a 10-mg i.v. dose of naltrexone and a 63-mg dose by subcutaneous implantation of the beads. Average plasma naltrexone levels were maintained at 0.3-0.4 ng/ml for approximately 1 month. Two out of three subjects experienced a local inflammatory reaction at the site of implantation. This unexplained problem prevented further clinical testing of... 

---