Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0451641 (urolithiasis)
 3,973 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe the first case of efavirenz-induced urolithiasis in a 47-year-old HIV-positive patient. Urinary obstruction led to pyelonephritis and septic shock, requiring emergency ureteral catheterisation. The subsequent clinical course was favourable, allowing the patient's discharge on day 5. A 7 mm, radio-translucent, non-crystalline, beige stone was extracted during catheterisation. Stone analysis by Fourier transform infrared spectrometry, liquid chromatography and mass spectrometry revealed a stone composed of efavirenz (EFV) metabolites M4, M5, M8 (as described by Mutlib et al. in 1999) and approximately 50% of unspecified proteins. EFV is a non-nucleoside reverse transcriptase inhibitor introduced to European markets in 1999. It is principally metabolised by cytochrome P450 3A4 and 2B6. Of the dose, 14-34% is excreted in the urine, 1% as unchanged drug. The patient had been taking 600 mg EFV per day for 3 years. As EFV-induced urolithiasis has not been reported so far, we would like to draw the attention of the medical community to this potentially severe complication.
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PMID:Efavirenz-induced urolithiasis. 1662 85

There are already about a dozen antiepileptic drugs with acceptable harm-benefit balances that can be used in combination therapy for adult patients whose partial epilepsy is not adequately controlled by successive single-agent regimens. Retigabine (Trobalt, GlaxoSmithKline) has now been authorised in the European Union in this indication. Clinical evaluation is based on 3 double-blind randomised controlled trials in which either retigabine or placebo was added to an ineffective ongoing treatment. An additional 30% of patients treated with retigabine (in absolute numbers) had at least a 50% reduction in the monthly frequency of seizures. This translates to approximately 50% of patients with a reduced seizure rate as compared with about 20% of patients on placebo. Based on indirect comparisons, which must be interpreted with care, this efficacy seems similar to that of other antiepileptic drugs. Retigabine shares several adverse effects with other antiepileptic drugs, especially neuropsychiatric disorders. Retigabine can also cause urinary disorders (5%), psychotic disorders (about 6%) and urolithiasis. It also appears to prolong the QT interval. Retigabine does not interfere with major cytochrome P450 isoenzymes or with P-glycoprotein-mediated drug transport. About 30% of the ingested dose is excreted unchanged in urine. The risk of pharmacokinetic interactions is low in patients with normal renal function. In practice, retigabine is another option for second-line combination therapy in patients at high risk of drug interactions.
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PMID:Retigabine: fewer drug interactions. 2242 81