Lack of response to monoclonal antibodies (mAbs) has been associated with inadequate mAb serum concentrations. Therapeutic drug monitoring (TDM) of mAbs has the potential to guide to more effective dosing in individual patients. This review discusses the mechanisms responsible for interpatient variability of mAb pharmacokinetics, summarizes exposure-response data of mAbs used in inflammatory and malignant disease, presents current evidence of mAb-TDM in inflammatory disease, and provides hurdles and required future steps for further implementing mAb-TDM.
Metformin is a worldwide used and effective antihyperglycemic agent. It is generally well tolerated but contra-indicated in severe renal dysfunction. Metformin does not cause hypoglycaemia, however this case describes hypoglycaemia after an overdose. Another well-known, but rare and potentially life-threatening complication of metformin is the occurrence of LA, the so-called metformin-associated lactic acidosis (MALA). The severe consequences of an overdose of metformin, as well as the pathophysiologic mechanisms and the clinical consequences of LA in combination with severe hypoglycaemia are described in this report. Early recognition and swift clinical intervention is of paramount importance in case of auto-intoxication with metformin to prevent a lethal outcome.
IntroductionSerum concentrations of acetaminophen are measured to predict the risk of hepatotoxicity in cases of acetaminophen overdose and to identify acetaminophen use in patients with acute liver injury without a known cause. The acetaminophen concentration determines if treatment with N-acetyl cysteine, the antidote for acetaminophen poisoning, is warranted.DescriptionA 49-year-old woman was admitted to our hospital with a hepatic encephalopathy and a total serum bilirubin concentration of 442 µmol/l. The acetaminophen concentration of 11.5 mg/l was measured with an enzymatic-colorimetric assay, thus treatment with N-acetyl cysteine was started. Interestingly, the acetaminophen concentration remained unchanged (11.5–12.3 mg/l) during a period of 4 consecutive days. In contrast, the acetaminophen concentration measured by HPLC, a chromatographic technique, remained undetectableDiscussionIn the presented case, elevated bilirubin was the most likely candidate to interfere with acetaminophen assay causing false positive results. Bilirubin has intense absorbance in the ultraviolet and visible regions of the electromagnetic spectrum and for that reason it causes interference in an enzymatic-colorimetric assay.ConclusionFalse positive acetaminophen laboratory test results may be found in icteric serum, when enzymatic-colorimetric assays are used for determination of an acetaminophen concentration. Questionable acetaminophen results in icteric serum should be confirmed by a non-enzymatic method, by means of ultrafiltration of the serum, or by dilution studies.
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