Plasma protein binding of frusemide in liver disease: effect of hypoalbuminaemia and hyperbilirubinaemia.

Viani, A; Carrai, Maura; Pacifici, Gian Maria

doi:10.1111/j.1365-2125.1989.tb05412.x

Cited by 6 publications

(3 citation statements)

References 11 publications

(8 reference statements)

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“…However, in chronic disease states, such as chronic hepatic dysfunction and CKD, the DDI indices of drugs should be higher because of an increased proportion of unbound drugs. Furthermore, patients with chronic hepatic dysfunction or CKD frequently have hypoalbuminemia, which also results in an increase in protein-unbound drugs (Viani et al, 1989;Meijers et al, 2008). It has also been reported that, compared with control subjects, dialysis patients have significantly lower levels of albumin (Małgorzewicz et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

Potential Drug Interactions Mediated by Renal Organic Anion Transporter OATP4C1

Sato¹,

Mishima²,

Mano³

et al. 2017

J Pharmacol Exp Ther

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Organic anion-transporting polypeptide 4C1 (OATP4C1) is an organic anion transporter expressed in the basolateral membrane of the renal proximal tubules. It plays a major role in the urinary excretion of both exogenous drugs and endogenous compounds. Our previous studies have indicated the importance of OATP4C1 in pathologic and physiologic conditions; however, the majority of its pharmacologic characteristics remained unclear. Therefore, to provide essential information for clinical drug therapy decisions and drug development, we clarified drug interactions mediated by OATP4C1. To elucidate potential drug interactions via OATP4C1, we screened 53 representative drugs commonly used in clinical settings. Next, we evaluated the IC values of drugs that inhibited OATP4C1 by more than 50%. To apply our results to clinical settings, we calculated the drug-drug interaction (DDI) indices. The screening analysis using an OATP4C1-expressing cell system demonstrated that 22 out of 53 therapeutic drugs inhibited OATP4C1-mediated triiodothyronine transport. In particular, OATP4C1-mediated transport was strongly inhibited by 10 drugs. The IC values of 10 drugs-nicardipine, spironolactone, fluvastatin, crizotinib, levofloxacin, clarithromycin, ritonavir, saquinavir, quinidine, and verapamil-obtained in this study were 51, 53, 41, 24, 420, 200, 8.5, 4.3, 100, and 110 M, respectively. The IC values of these drugs were higher than the plasma concentrations obtained in clinical practice. However, ritonavir showed the highest DDI index (1.9) for OATP4C1, suggesting that it may strongly influence this transporter and thus cause drug interactions seen in clinical settings. Our finding gives new insight into the role of OATP4C1 in clinical DDIs.

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Section: Discussionmentioning

confidence: 99%

Potential Drug Interactions Mediated by Renal Organic Anion Transporter OATP4C1

Sato¹,

Mishima²,

Mano³

et al. 2017

J Pharmacol Exp Ther

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“…A sharp rise in bilirubin saturates the binding sites on serum protein, thus reducing the availability for phenytoin and potentiating free phenytoin concentration. This effect has been demonstrated with other protein-bound drugs in patients with a similarly deranged biochemical picture 5 6…”

Section: Discussionmentioning

confidence: 63%

When less is more: a case of phenytoin toxicity

2013

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The authors present a case of an 87-year-old gentleman who presented with general deterioration, increased confusion, recurrent falls and unsteadiness. He was treated for a urinary tract infection but was found to deteriorate rapidly, developing bilateral nystagmus, marked pastpointing, dysarthria and central ataxia. He had a complex medical history including epilepsy controlled with long-term phenytoin. Phenytoin is 90% protein bound and displaced by bilirubin. At the time of deterioration his total phenytoin concentration was within the limits of the laboratory's recommended therapeutic range. The biochemistry report also denoted the patient was hypoalbuminaemic and hyperbilirubinaemic. His symptoms completely resolved with phenytoin dose reduction. The combination of low albumin and high bilirubin may cause an increase in the free phenytoin concentration, resulting in toxicity, despite the measured total phenytoin concentration being within the therapeutic interval.

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“…Furosemide protein-binding alterations occurred in the presence of liver dysfunction but only when bilirubin concentrations exceeded 4 mg/dL and/or at albumin concentrations less than 3 g/dL. 20 This study did not measure furosemide blood concentrations. Further investigation of this topic is warranted.…”

Section: Review Of the Literaturementioning

confidence: 87%

Acute Sensorineural Hearing Loss: Furosemide Ototoxicity Revisited

Baldwin

Budzinski

Shapiro³

2008

Hosp Pharm

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Background Acquired sensorineural hearing loss occurs as a consequence of damage to the inner ear and may result from tumors, medications, or noise-induced acoustic trauma. Furosemide ototoxicity—manifested by tinnitus, vertigo, or hearing loss—is frequently reversible, but some cases may result in permanent hearing loss. Purpose Because of the serious nature of this adverse drug reaction, the intent of this article is heightening the awareness of furosemide-induced ototoxicity through case presentation. Methods An updated review of the literature is provided. Results and Conclusion The case demonstrates multiple risk factors that can be used to empower readers for identification of patients who are also at high risk. Strategies are presented for avoiding further cases.

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Plasma protein binding of frusemide in liver disease: effect of hypoalbuminaemia and hyperbilirubinaemia.

Cited by 6 publications

References 11 publications

Potential Drug Interactions Mediated by Renal Organic Anion Transporter OATP4C1

Potential Drug Interactions Mediated by Renal Organic Anion Transporter OATP4C1

When less is more: a case of phenytoin toxicity

Acute Sensorineural Hearing Loss: Furosemide Ototoxicity Revisited

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