Drug toxicity clinical side effects

This royal-blue-colored drug is an anthracenedione that inhibits DNA topoisomerase II. The pharmacokinetics of mitoxantrone may best be described by a three-compartment model, with an a half-life of 3 to 10 minutes, a 3 half life of 0.3 to 3 hours, and a median terminal half-life of 12 days. Biliary elimination appears to be the primary route of elimination, with less than 10% of the drug eliminated by the kidney.23 Mitoxantrone has shown clinical activity in the treatment of acute leukemias, breast and prostate cancer, and non-Hodgkin s lymphomas. Myelosuppression, mucositis, nausea and vomiting, and cardiac toxicity are side effects of this drug. The total cumulative dose limit is 160 mg/m2 for patients who have not received prior anthracycline or mediastinal radiation. Patients who have received prior doxorubicin or daunorubicin therapy should not receive a cumulative dose greater than 120 mg/m2 of mitoxantrone. Patients should be counseled that their urine will turn a blue-green color. 

Product quality, purity and consistency are critically important in the pharmaceutical sector, applying to all stages of the supply chain and final dosed product. The human body is an exceptionally complex system and the full effect of a pharmaceutical product, consisting of the API, impurities and formulation components, is impossible to predict from first principles. The industry relies on rigorous clinical trials to assess drug efficacy, toxicity and side effect profiles. 

Enzyme Induction (CYP3A4) and Drug Design 1119 Tab. 8.4 Clinical toxicities and side-effects of P4503A4 inducers. 

Drug repurposing maximises the benefit of existing drugs of proven provenance or compounds that have only failed late-phase clinical trials for indication-specific efficacy reasons, not safety concerns. Most, maybe all, drugs have significant off-target activity, thus potential new therapeutic uses should be identifiable for molecules known to be free of toxicity or side-effects. 

Q[n] and drug delivery are emerging as an exciting area in the supramolecular context. Q[n] have the potential to contribute to the resolution of some drug delivery difficulties that include bioavailability, bio and chemical stability, improvements in efficacy and efficiency, limiting toxicity, and side effects. In relative terms, only a few examples of this potential have so far been realized. As we increase our understanding of the physical and chemical capabilities of Q[n] and develop new derivatives and supramolecular forms, Q[n] will be one of the drug delivery tools used in the clinic in future. 

Out of the numerous compounds these investigators made, they eventually selected /S-hydroxyethyla oquinine for clinical trial owing to its low toxicity, relatively high bacteriostatic power and lack of deleterious side-effects. The following table summarises the data available on these two points for this drug and its near relatives. The name opocupreine is used by Cretcher for opoquinine (p. 452). 

Drugs can only be effective if enough is present at the target site and they can be harmful if too much is present so as to produce toxic side effects. Any attempt to draw conclusions about the clinical efficacy of a drug in a clinical trial without knowledge of the concentration at the target site is premature. The science of pharmacokinetics basically... 

From pilot studies carried out in the clinic with the NNRTIs TIBO R82913 [75] and pyridinone L-697,661 [76], it appears that the compounds are well tolerated and do not cause toxic side effects. Most of the HIV-1 isolates obtained from the patients treated with TIBO R82913 appeared to be as sensitive to the compound as wild-type virus only two HIV-1 variants were isolated, showing a sensitivity that was reduced 20-fold or more than 100-fold, the latter being caused by a mutation (Tyr —> Leu) at position 188 of the RT [77]. In fact, the latter mutation was lost upon passaging the virus in vitro in cord blood lymphocytes. Following treatment of the patients with pyridinone L-697,661, drug-resistant HIV-1 variants appeared that contained mutations at the RT positions 103 (Lys —> Asn) and 181 (Tyr —> Cys) [76]. 

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