Theophylline precipitated alterations of lithium clearance

Perry, Paul J.; Calloway, Rachel; Cook, Brian L.; Smith, Robert E.

doi:10.1111/j.1600-0447.1984.tb02527.x

Cited by 32 publications

(8 citation statements)

References 6 publications

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“…In this context it is important to note that methylxanthine drugs caffeine and theophylline that increase NHA2 levels are well known to promote Li + clearance via kidney. These drugs enhance renal salt and water transport and are contraindicated for Li + therapy (48,49). Using ratiometric Fura 2 Ca 2+ imaging, we first confirmed significant increase in cytoplasmic Ca 2+ with caffeine and theophylline treatment in MDCK cells ( Fig.…”

Section: Potential Modulation Of Kidney Function By Drug and Hormonalmentioning

confidence: 59%

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NHA2 promotes cyst development in an in vitro model of polycystic kidney disease

Prasad

Dang

Kondapalli

et al. 2018

Preprint

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Key pointsr Significant and selective up-regulation of the Na + /H + exchanger NHA2 (SLC9B2) was observed in cysts of patients with autosomal dominant polycystic kidney disease.r Using the MDCK cell model of cystogenesis, it was found that NHA2 increases cyst size.Silencing or pharmacological inhibition of NHA2 inhibits cyst formation in vitro.r Polycystin-1 represses NHA2 expression via Ca 2+ /NFAT signalling whereas the dominant negative membrane-anchored C-terminal fragment (PC1-MAT) increased NHA2 levels.r Drugs (caffeine, theophylline) and hormones (vasopressin, aldosterone) known to exacerbate cysts elicit NHA2 expression.r Taken together, the findings reveal NHA2 as a potential new player in salt and water homeostasis in the kidney and in the pathogenesis of polycystic kidney disease.Abstract Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in PKD1 and PKD2 encoding polycystin-1 (PC1) and polycystin-2 (PC2), respectively. The molecular pathways linking polycystins to cyst development in ADPKD are still unclear. Intracystic fluid secretion via ion transporters and channels plays a crucial role in cyst expansion in ADPKD. Unexpectedly, we observed significant and selective up-regulation of NHA2, a member of the SLC9B family of Na + /H + exchangers, that correlated with cyst size and disease severity in ADPKD patients. Using three-dimensional cultures of MDCK cells to model cystogenesis in vitro, we showed that ectopic expression of NHA2 is causal to increased cyst size. Induction of PC1 in MDCK cells inhibited NHA2 expression with concordant inhibition of Ca 2+ influx through store-dependent and -independent pathways, whereas reciprocal activation of Ca 2+ influx by the dominant negative membrane-anchored C-terminal tail fragment of PC1 elevated NHA2. We showed that NHA2 is a target of Ca 2+ /NFAT signalling and is transcriptionally induced by

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Section: Potential Modulation Of Kidney Function By Drug and Hormonalmentioning

confidence: 59%

“…Caffeine is also thought to promote cyst development in PKD patients (43). Furthermore, caffeine and theophylline are well known to promote clearance of lithium through kidney (48,49). Given our previous findings that NHA2 is an important cellular lithium efflux transporter (17)…”

Section: Discussionmentioning

confidence: 91%

NHA2 promotes cyst development in an in vitro model of polycystic kidney disease

Prasad

Dang

Kondapalli

et al. 2018

Preprint

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“…Besides use and start of potentially interacting co‐medication, the withdrawal of these agents could also influence lithium serum levels. However, it has been reported that withdrawal is more likely to result in a decrease (12–38) rather than in an increase in lithium serum level. As our focus is on the appearance of elevated lithium serum levels, data on withdrawal of potentially interacting drugs was of lesser importance to this report.…”

Section: Discussionmentioning

confidence: 99%

Drug‐drug interactions as a determinant of elevated lithium serum levels in daily clinical practice

et al. 2005

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Objective: Lithium is a drug with a narrow therapeutic window. Concomitantly used medication is a potentially influencing factor of lithium serum concentrations. We conducted a multicentre retrospective case‐control study with the aim of investigating lithium‐related drug interactions as determinants of elevated lithium serum levels in daily clinical practice. Methods: Cases were patients with an increase of at least 50% in lithium serum concentrations resulting in an elevated lithium serum level of at least 1.3 mmol/L, and who were not suspected of a suicide attempt. Controls were patients who showed stable lithium serum levels within the therapeutic range. Use and start of non‐steroidal anti‐inflammatory drugs, diuretics, renin–angiotensin inhibitors, theophyllin and antibiotics were investigated as potential determinants of the elevated lithium serum levels. Irregularity in lithium dispensing pattern, change in lithium dosing regimen, age, gender, prescribing physician and laboratory parameters were investigated as potential confounders. Results: We included 51 cases and 51 controls in our study. Five (9.8%) controls and 15 (29.4%) cases used potentially interacting co‐medication [OR of 3.83 (95%CI 1.28–11.48)]. Start of potentially interacting co‐medication was observed in eight (15.7%) cases and in zero (0%) controls resulting in an OR of 20.13 (95% CI 1.13–359). After adjustment for co‐medication, irregularity in lithium dispensing pattern, change in lithium dosing regimen, and age, the statistically significant association was lost. We report an OR of 2.70 (95% CI 0.78–9.31) for use of concomitant medication, with a large contribution of antibiotic agents, and an OR of 3.14 (95% CI 1.15–8.61) for irregularity in lithium dispensing pattern. Conclusion: Use of co‐medication, especially antibiotics, tends to be associated with elevated lithium serum levels.

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“…In ten healthy subjects with normal renal function administered lithium carbonate 900mg daily for 7 days, the addition of theophylline to achieve steadystate plasma concentrations of between 5 and 12mg/1 significantly (P < 0.05) increased the renal clearance of lithium by an average of 42% from 18.3 ± 7.0 to 26.1 ± 11.5mllmin and shortened the half-life from 28.1 ± 7.5 to 21.8 ± 6.6h (PERRY et al 1984). There was also a significant decrease in serum lithium concentrations by an average of 30%.…”

Section: A) Theophyllinementioning

confidence: 99%

Mechanisms of Drug Interactions

Amidon¹,

D’Arcy²,

McElnay³

et al. 1996

Handbook of Experimental Pharmacology

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softcover reprint of the hardcover 1st edition 1996 PrefaceOver the years a number of excellent books have classified and detailed drugdrug interactions into their respective categories, e.g. interactions at plasma protein binding sites; those altering intestinal absorption or bioavailability; those involving hepatic metabolising enzymes; those involving competition or antagonism for receptor sites, and drug interactions modifying excretory mechanisms. Such books have presented extensive tables of interactions and their management. Although of considerable value to clinicians, such publications have not, however, been so expressive about the individual mechanisms that underlie these interactions.It is within this sphere of "mechanisms" that this present volume specialises. It deals with mechanisms of in vitro and in vivo, drug-drug, drugfood and drug-herbals interactions and those that cause drugs to interfere with diagnostic laboratory tests. We believe that an explanation of the mechanisms of such interactions will enable practitioners to understand more fully the nature of the interactions and thus enable them to manage better their clinical outcome.If mechanisms of interactions are better understood, then it may be possible for the researcher to develop meaningful animal/biochemical/tissue culture or physicochemical models to which new molecules could be exposed during their development stages. The present position, which largely relies on patients experiencing adverse interactions before they can be established or documented, can hardly be regarded as satisfactory.This present volume is classified into two major parts; firstly, pharmacokinetic drug interactions and, secondly, pharmacodynamic drug interactions. Within these parts, we have been fortunate to enlist the help of acknowledged experts in preparing specific chapters focusing on aspects of the interaction spectrum.We believe that this volume will add much to that which is currently known about drug interactions and will directly enhance the safer use of medicines.

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Theophylline precipitated alterations of lithium clearance

Cited by 32 publications

References 6 publications

NHA2 promotes cyst development in an in vitro model of polycystic kidney disease

NHA2 promotes cyst development in an in vitro model of polycystic kidney disease

Drug‐drug interactions as a determinant of elevated lithium serum levels in daily clinical practice

Mechanisms of Drug Interactions

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