tact sensitization could not be induced. Clinically, adverse reactions are also rare. In our 5 additional cases, sensitization became apparent after periods of treatment from 2 to 10 months. We detected no contact sensitization to other ingredients of bufexamac preparations. In all cases, sensitization was clinically relevant. As found before (8), most of our patients had long-standing eczemas, perhaps enhancing the risk of sensitization. In patients with exacerbations of long-standing eczemas, contact allergy to bufexamac should be considered. Testing with bufexamac 5% pet. is appropriate.

Occupational airborne allergic contact dermatitis from mesna.

This review discusses several issues in the clinical pharmacology of the antitumour agent ifosfamide and its metabolites. Ifosfamide is effective in a large number of malignant diseases. Its use, however, can be accompanied by haematological toxicity, neurotoxicity and nephrotoxicity. Since its development in the middle of the 1960s, most of the extensive metabolism of ifosfamide has been elucidated. Identification of specific isoenzymes responsible for ifosfamide metabolism may lead to an improved efficacy/toxicity ratio by modulation of the metabolic pathways. Whether ifosfamide is specifically transported by erythrocytes and which activated ifosfamide metabolites play a key role in this transport is currently being debated. In most clinical pharmacokinetic studies, the phenomenon of autoinduction has been observed, but the mechanism is not completely understood. Assessment of the pharmacokinetics of ifosfamide and metabolites has long been impaired by the lack of reliable bioanalytical assays. The recent development of improved bioanalytical assays has changed this dramatically, allowing extensive pharmacokinetic assessment, identifying key issues such as population differences in pharmacokinetic parameters, differences in elimination dependent upon route and schedule of administration, implications of the chirality of the drug and interpatient pharmacokinetic variability. The mechanisms of action of cytotoxicity, neurotoxicity, urotoxicity and nephrotoxicity have been pivotal issues in the assessment of the pharmacodynamics of ifosfamide. Correlations between the new insights into ifosfamide metabolism, pharmacokinetics and pharmacodynamics will rationalise the further development of therapeutic drug monitoring and dose individualisation of ifosfamide treatment.

Clinical Pharmacokinetics and Pharmacodynamics of Ifosfamide and its Metabolites

The toxicity profile of the alkylating anti-cancer drug ifosfamide is quite well known. However, up to now only a few cases of hypersensitivity as an attributed adverse effect of ifosfamide have be...

Hypersensitivity after ifosfamide administration

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Hypersensitivity after ifosfamide administration