Parental Drug Association

Parental Drug Association. Points to consider for cleaning validation. PDA technical report no. 29.52(6), 1998. 

L. Torbeck, Determining the number of retests for OOS, presented at Parental Drug Association Course on Handling OOS Results, May 1999. 

A. P. MacKenzie, Basic principles of freeze-drying for pharmaceuticals. Ann. Meeting of the Parenteal Drug Association in New York, October 20th, 1972. 

Agalloco J Validation— yesterday, today and tomorrow. Proceedings of Parenteral Drug Association International Symposium. Basel, Switzerland Parental Drug Association, 1993. 

The MS-MS data from metabolite 5 shows a base peak at m/z 437, at an increase of 16 Da over the parent drug, but, in common with Indinavir, ions at m/z 364 and 465. Of most significance is the ion at m/z 465 which indicates that the extra oxygen atom is associated with the indan ring structure. 

In an attempt to understand further the carcinogenicity of azathioprine, recent work in the authors laboratory has concentrated on the photodegradation of two compounds associated with the drug. l-Methyl-4-nitro-5-thioimid-azole is a metabolite and 5-hydroxy- l-methyl-4-nitroimidazole a hydrolysis product. Both gave, on irradiation at wavelengths greater than 300 nm, 1-methylparabanic acid (248) [152], The primary metabolites of azathioprine had previously been shown to be more potent than the parent drug as photosensitizers. Both 6-mercaptopurine and these imidazoles may play roles in its neoplastic action [151]. 

Based on the observation that pefloxacin (iV-methylnorfloxacin) exhibits enhanced in vivo activity upon oral administration (although it is less active in vitro) relative to norfloxacin, the same promoiety was investigated as an approach to blocking the secondary amine group, which seems to be associated with reduced oral absorption. Indeed, compound (78) was shown to produce about 5-fold higher serum levels of norfloxacin, after oral administration to mice than did the parent drug, itself. 

The route of administration of an NCE is typically the intended clinical route of administration. However, an alternative route may be used if this leads to an increase in systemic exposure of parent drug or major metabolites or if this alternative route satisfies another important objective of the study. For example, it is common to increase the exposure following inhalation administration by associating a subcutaneous administration of the NCE. 

Antihistamines, nonsedating/Cisapride/Pimozide- Cisapride and pimozide are metabolized by the cytochrome P-450 3A4 isozyme inhibitors of 3A4 can block the metabolism of these drugs, resulting in increased plasma concentrations of parent drug, which is associated with QT prolongation and with rare cases of serious cardiovascular adverse events, including death, because of ventricular tachycardia of the torsades de pointes type. In vitro, nefazodone inhibits 3A4. It is recommended that nefazodone not be used in combination with cisapride or pimozide. 

The thermal stability of oxfendazole has been examined in both water and cooking oil (88). Some evidence of instability was observed in boiling water after 3 h. This instability was associated with hydrolysis of the carbamate group of the oxfendazole molecule and formation of an amine byproduct. In hot cooking oil at 150 C or 180 C, the half-life of oxfendazole was 15 min or 6 min, respectively. The instability was also associated with the formation of the amine byproduct, which increased as the concentration of the parent drug decreased. 

It was later reported that both metabolic activation (reduction of the endoperoxide bridge) and the deactivation (hydroxylation plus O-glucuronylation) of arteflene occur in the rat liver. The balance of these pathways is associated with cytotoxicity, although only at relatively high concentrations in the cultured hepatocyte. The hepatic metabolism may restrict the therapeutic effectiveness of arteflene because 8-hydroxyarteflene retains only about 25% of the parent drug s antimalarial activity, while the enone is inactive <2004173>. 

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