title: Monitoring metformin in cardiac patients exposed to contrast media using ultra-high-performance liquid chromatography tandem mass-spectrometry.
abstract: BACKGROUND
  There is no evidence that the use of contrast media (CM) in diabetic patients with serum creatinine <130 μmole/L leads to metformin accumulation and subsequent lactic acidosis. Therefore, the objective of this investigation was to monitor cardiac patients for the effects of CM on their metformin plasma concentration and serum creatinine clearance (ClCr).
  
  
  METHODS
  Metformin plasma concentrations were measured by a new, fully validated specific, precise, and accurate ultra-high-performance liquid chromatography tandem mass-spectrometric assay. The detection was performed using positive electrospray ionization in the multiple reaction monitoring mode. Fifty patients with serum creatinine levels <130 μmole/L were monitored for the effect of CM exposure on metformin concentration and ClCr. Pharmacokinetic parameters were calculated in 8 of these patients, and metformin accumulation was monitored in 10 patients before and after their exposure to CM.
  
  
  RESULTS
  Linear response (r ≥ 0.998) was observed over the range of 5-2000 ng/mL of metformin, with the lower limit of quantification of 2.3 ng/mL. The intraday and interday precision (relative standard deviation) values were <13%, and the accuracy (relative error) was <-10% for metformin concentrations. The assay was sensitive to follow the pharmacokinetics of metformin in humans during a dosing interval after an oral dose at steady state. Metformin pharmacokinetic parameters were estimated in 8 patients exposed to CM. The mean C(max) of 1.9 ± 0.6 mg/L was attained at 4.1 ± 1.9 hours. There was no evidence of any drug accumulation or altered elimination due to the exposure to CM in the current population. ClCr showed no significant difference (P > 0.05) before (92.8 ± 11.3 mL/min) and after 48 hours (90.5 ± 10.5 mL/min) of exposure to CM.
  
  
  CONCLUSIONS
  Our data suggest that the recommendation to withhold metformin in diabetic patients during CM exposure could be revised to withholding the drug only in patients with moderate to severe renal dysfunction.
authors: Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Saudi Arabia. mradwan@pnu.edu.sa
authors: Mahasen A
authors: MA
authors: Radwan
authors: Esraa S
authors: ES
authors: Al Taweel
authors: Abdulrahman M
authors: AM
authors: Al-Moghairi
authors: Nouf M
authors: NM
authors: Aloudah
authors: Muneera A
authors: MA
authors: Al Babtain
authors: Hussein S
authors: HS
authors: Al-Amri
mesh_terms: D000140:Acidosis, Lactic / Q000517:prevention & control; D006328:Cardiac Catheterization / Q000009:adverse effects; D002851:Chromatography, High Pressure Liquid; D003287:Contrast Media / Q000009:adverse effects / Q000494:pharmacology*; D003404:Creatinine / Q000097:blood; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000150:complications; D004347:Drug Interactions; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D006331:Heart Diseases / Q000150:complications / Q000175:diagnosis*; D006801:Humans; D007004:Hypoglycemic Agents / Q000097:blood* / Q000493:pharmacokinetics; D057230:Limit of Detection; D008297:Male; D008687:Metformin / Q000097:blood* / Q000493:pharmacokinetics; D008875:Middle Aged; D051437:Renal Insufficiency / Q000150:complications; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry
chemical_list: D003287:Contrast Media; D007004:Hypoglycemic Agents; D008687:Metformin; D003404:Creatinine