Enantioselective Effect of Flurbiprofen on Lithium Disposition in Rats

Uwai, Yuichi; Matsumoto, Masashi; Kawasaki, Tatsuya; Nabekura, Tomohiro

doi:10.1159/000455917

Cited by 4 publications

(7 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The plasma concentrations of lithium were in the therapeutic range (Table 2). The renal clearance and the fractional excretion of lithium of the control group (Table 2) were comparable to our previous values that were obtained from the experiments with the lithium injection as a bolus [15,16]. Fanconi syndrome decreased the renal clearance of lithium, and no effect on the fractional excretion of lithium was recognized (Table 2).…”

Section: Discussion/conclusionsupporting

confidence: 85%

“…The correlation coefficient between creatinine clearance and lithium clearance of 303 data from 90 patients was calculated to be 0.4548 [25], and it is suggested that creatinine clear-ance may be a poor surrogate for the renal clearance of lithium exceptionally. In the previous and the present studies, we showed that the renal clearance of lithium was decreased by S-flurbiprofen, renal ischemia, and Fanconi syndrome in rats [15,16]. And, S-flurbiprofen decreased the fractional excretion of lithium, and no effect of renal ischemia and Fanconi syndrome on the ratio was recognized [15,16].…”

Section: Discussion/conclusionsupporting

confidence: 56%

See 1 more Smart Citation

Effect of Experimental Fanconi Syndrome on Tubular Reabsorption of Lithium in Rats

Uwai¹,

Nabekura²

2021

Pharmacology

Self Cite

View full text Add to dashboard Cite

Lithium, administered to patients of bipolar disorders, is mainly excreted into urine, and tubular reabsorption at the proximal tubule is involved in the renal handling of lithium. In this study, we examined the renal excretion of lithium in rats with Fanconi syndrome, characterized by defects of transports of various compounds at the proximal tubules, induced by maleic acid. After maleic acid was intravenously injected, mannitol and lithium chloride were infused in turn. Using samples of plasma and bladder urine during the mannitol infusion, renal parameters were determined. Pharmacokinetic parameters of lithium were obtained using samples during the lithium chloride infusion. Maleic acid decreased creatinine clearance and increased the fractional excretion of glucose and phosphate, suggesting the induction of Fanconi syndrome. In rats with Fanconi syndrome, plasma concentration of lithium was increased, and its renal clearance was decreased. No effect on the fractional excretion of lithium was exhibited. This study represents that the tubular reabsorption of lithium was impaired to the same degree with glomerular filtration in rats with experimental Fanconi syndrome and that the dysfunction of the tubular reabsorption of glucose and phosphate was more severe. It is possible that Fanconi syndrome inhibited the reabsorption of lithium at the proximal tubule and facilitated the reabsorption of lithium from the loop of Henle to the collecting duct.

show abstract

Section: Discussion/conclusionsupporting

confidence: 85%

Section: Discussion/conclusionsupporting

confidence: 56%

Effect of Experimental Fanconi Syndrome on Tubular Reabsorption of Lithium in Rats

Uwai¹,

Nabekura²

2021

Pharmacology

Self Cite

View full text Add to dashboard Cite

show abstract

“…This implies that the decline of the lithium reabsorption is not parallel with that of glomerular filtration in patients with renal failure. Our recent report indicated a decrease of the fractional excretion of lithium as well as C cr by (S)‐flurbiprofen in rats (Uwai et al, ). This suggests a lesser impairment of lithium reabsorption in comparison with the glomerular filtration in rats administered (S)‐flurbiprofen.…”

Section: Resultsmentioning

confidence: 92%

“…Recently, we examined the effect of each enantiomer of flurbiprofen, reported to increase the plasma concentration of lithium in patients with bipolar disorder (Hughes, Small, Brink, & McKenzie, ), on the renal handling of lithium in rats. The (S)‐enantiomer reduced creatinine clearance (C cr ) and the renal clearance of lithium (Li CL r ) in rats, and in particular, a significant decrease in the ratio of Li CL r to C cr was exhibited (Uwai, Matsumoto, Kawasaki, & Nabekura, ). The findings suggested that the damage to glomerular filtration by (S)‐flurbiprofen was greater than that to lithium reabsorption in the rats, and we considered it important to collect data regarding the renal handling of lithium in rats with various renal failures.…”

Section: Introductionmentioning

confidence: 99%

Effect of renal ischemia on urinary excretion of lithium in rats

Uwai

Suzuki

Kondo

et al. 2018

Biopharm & Drug Disp

Self Cite

View full text Add to dashboard Cite

Lithium, administered to patients with bipolar disorders, is mainly excreted in the urine, and tubular reabsorption is involved. This study characterized the renal excretion of lithium in rats subjected to renal ischemia for 60 min or 90 min. After intravenous injection of lithium chloride at 25 mg/kg, the pharmacokinetic parameters of lithium were determined. In sham‐operated rats, the renal clearance of lithium was calculated to be 1.49 ml/min/kg, and its ratio to creatinine clearance (fractional excretion) was 43.4%. Renal ischemia inhibited the renal excretion of lithium, and did not affect its fractional excretion. The urinary pH of rats with renal ischemia for 90 min was significantly higher than those of the other groups, and the linear regression with the fractional excretion of lithium in rats with renal ischemia showed a moderate correlation (r = 0.650, p = 0.00193). This study demonstrated the effect of renal ischemia on the renal excretion of lithium in rats. It was suggested that not only glomerular filtration but also the reabsorption of lithium was impaired by renal ischemia.

show abstract

“…The ( S )-enantiomer of naproxen is commercially available. We examined the enantioselective effects of flurbiprofen on the disposition of lithium in rats, and demonstrated that the ( S )-enantiomer, but not the ( R )-enantiomer, decreased the renal clearance of lithium with the impairment of renal function [2]. The anticoagulant drug warfarin is also chiral.…”

Section: Introductionmentioning

confidence: 99%

Enantioselective Drug Recognition by Drug Transporters

Uwai

2018

Molecules

Self Cite

View full text Add to dashboard Cite

Drug transporters mediate the absorption, tissue distribution, and excretion of drugs. The cDNAs of P-glycoprotein, multidrug resistance proteins (MRPs/ABCC), breast cancer resistance protein (BCRP/ABCG2), peptide transporters (PEPTs/SLC15), proton-coupled folate transporters (PCFT/SLC46A1), organic anion transporting polypeptides (OATPs/SLCO), organic anion transporters (OATs/SLC22), organic cation transporters (OCTs/SLC22), and multidrug and toxin extrusions (MATEs/SLC47) have been isolated, and their functions have been elucidated. Enantioselectivity has been demonstrated in the pharmacokinetics and efficacy of drugs, and is important for elucidating the relationship with recognition of drugs by drug transporters from a chiral aspect. Enantioselectivity in the transport of drugs by drug transporters and the inhibitory effects of drugs on drug transporters has been summarized in this review.

show abstract

Enantioselective Effect of Flurbiprofen on Lithium Disposition in Rats

Cited by 4 publications

References 10 publications

Effect of Experimental Fanconi Syndrome on Tubular Reabsorption of Lithium in Rats

Effect of Experimental Fanconi Syndrome on Tubular Reabsorption of Lithium in Rats

Effect of renal ischemia on urinary excretion of lithium in rats

Enantioselective Drug Recognition by Drug Transporters

Contact Info

Product

Resources

About