Effect of Clarithromycin on the Pharmacokinetics of Cabergoline in Healthy Controls and in Patients With Parkinson’s Disease

Nakatsuka, Akiko; Nagai, Masahiro; Yabe, Hayato; Nishikawa, Noriko; Nomura, Takuo; Moritoyo, Hiroyoko; Moritoyo, Takashi; Nomoto, Masahiro

doi:10.1254/jphs.fp0050711

Cited by 22 publications

(9 citation statements)

References 25 publications

(20 reference statements)

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“…In one case, a 300% increase in cabergoline concentration without associated toxicity was reported, and in the second, cabergoline toxicity in the form of hyperkinesia requiring cabergoline dose reduction subsequently occurred. In the second paper, a pharmacokinetic study evaluating co‐administration of clarithromycin and cabergoline in ten healthy adults and seven patients with PD demonstrated that clarithromycin resulted in mean cabergoline concentration increases to about 2.6‐fold and 1.7‐fold in healthy volunteers and PD patients respectively . There was no dose‐related adverse event reported in this paper, however, three of seven PD patients experienced improvement in parkinsonian symptoms.…”

Section: Discussionmentioning

confidence: 63%

“…There was no dose‐related adverse event reported in this paper, however, three of seven PD patients experienced improvement in parkinsonian symptoms. While investigators of these reports attribute the mechanism of interaction as itraconazole/clarithromycin‐mediated inhibition of the CYP3A4 metabolism of cabergoline, it has subsequently been hypothesized to have occurred as a result of inhibition of the P‐gp transporter (a transporter which both clarithromycin and itraconazole are known to inhibit), which is responsible for the efflux of cabergoline from the CNS .…”

Section: Discussionmentioning

confidence: 99%

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Cabergoline: a review of its use in the inhibition of lactation for women living with HIV

et al. 2019

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Introduction In developed countries, breastfeeding is not recommended for women living with human immunodeficiency virus (WLWH). However, lactation symptoms can be distressing for women who choose not to breastfeed. There is currently no universal guideline on the most appropriate options for prevention or reduction of lactation symptoms amongst WLWH. This review describes the evidence base for using cabergoline, a dopaminergic agonist, for the post‐partum inhibition of lactation for WLWH. Methods A scoping review of post‐partum pharmaceutical lactation inhibition specific for WLWH was conducted using searches in PubMed, Medline Ovid, EBM Reviews Ovid, Embase, Web of Science and Scopus until 2019. A narrative review of cabergoline pharmacologic properties, therapeutic efficacy, tolerability data and drug interaction data relevant to lactation inhibition was then conducted. Results and discussion Among 1366 articles, the scoping review identified 13 relevant publications. Eight guidelines providing guidance regarding lactation inhibition for WLWH and two surveys of medical practice on this topic in UK have been published. Three studies have evaluated the use of pharmaceutical agents in WLWH. Two of these studies evaluated cabergoline and reported it to be an effective method of lactation inhibition in this population. The third study evaluated ethinyl estradiol and bromocriptine use and showed poor efficacy. Cabergoline is a long‐acting dopamine D2 agonist and ergot derivative that inhibits prolactin secretion and suppresses physiologic lactation when given as a single oral dose of 1 mg after delivery. Cabergoline is at least as effective as bromocriptine for lactation inhibition with success rates between 78% and 100%. Transient, mild to moderate adverse events to cabergoline are described in clinical trials. Few drug interactions exist as cabergoline is neither a substrate nor an inducer/inhibitor of hepatic cytochrome P450 isoenzymes. There are no reported clinically significant drug–drug interactions between cabergoline and any antiretroviral medications including protease inhibitors. Conclusions Cabergoline is a safe and effective pharmacologic option for the prevention of physiological lactation and associated physical symptoms in non‐breastfeeding women. Future studies should focus on its safety, efficacy and acceptability among WLWH.

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Section: Discussionmentioning

confidence: 63%

Section: Discussionmentioning

confidence: 99%

Cabergoline: a review of its use in the inhibition of lactation for women living with HIV

et al. 2019

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“…Cabergoline PK was studied in 10 healthy volunteers and 7 Parkinson patients after co-administration of CLR. This resulted in an increase of both the AUC and C max of cabergoline by 260% in healthy volunteers and by 170% in Parkinson patients [232]. When ERY was co-administered with roflumilast, the AUC of the latter increased by 70% in an open-label single-dose comparative study of 16 healthy subjects [233].…”

Section: Resultsmentioning

confidence: 99%

Pharmacokinetic Drug Interactions of Antimicrobial Drugs: A Systematic Review on Oxazolidinones, Rifamycines, Macrolides, Fluoroquinolones, and Beta-Lactams

et al. 2011

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Like any other drug, antimicrobial drugs are prone to pharmacokinetic drug interactions. These drug interactions are a major concern in clinical practice as they may have an effect on efficacy and toxicity. This article provides an overview of all published pharmacokinetic studies on drug interactions of the commonly prescribed antimicrobial drugs oxazolidinones, rifamycines, macrolides, fluoroquinolones, and beta-lactams, focusing on systematic research. We describe drug-food and drug-drug interaction studies in humans, affecting antimicrobial drugs as well as concomitantly administered drugs. Since knowledge about mechanisms is of paramount importance for adequate management of drug interactions, the most plausible underlying mechanism of the drug interaction is provided when available. This overview can be used in daily practice to support the management of pharmacokinetic drug interactions of antimicrobial drugs.

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“…The cardinal treatment for patients with PD is oral administration of levodopa with peripheral decarboxylase inhibitor (DCI). 1 There are two DCI in clinical use: benserazide and carbidopa. In combination with levodopa, they are generally regarded as equally effective.…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics of levodopa/benserazide versus levodopa/carbidopa in healthy subjects and patients with Parkinson's disease

Iwaki

Nishikawa

Nagai

et al. 2014

Neurology & Clinical Neurosc

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Background There are two formulations of levodopa in Japan and a few other countries, levodopa/benserazide 100/25 mg and levodopa/carbidopa 100/10 mg, which have been generally regarded as interchangeable in Parkinson's disease treatment. Aim We investigated the pharmacokinetics of levodopa in the two kinds of levodopa/decarboxylase inhibitor (benserazide or carbidopa) formulations to study their equivalence. Methods Population pharmacokinetic analysis was carried out using levodopa data from the healthy subject study and, additionally, for 70 plasma concentration data points from Parkinson's disease patients receiving either levodopa/decarboxylase inhibitor combination in clinical practice. Results In healthy subjects, the mean ± standard deviation plasma levodopa maximum observed plasma concentration and area under the plasma concentration time curve from time 0 to 3 h (512 ± 139 vs 392 ± 49 μmol•h/L, P < 0.05) were significantly higher after levodopa/benserazide compared with levodopa/carbidopa. Levodopa time to maximum observed plasma concentration and plasma elimination half‐life were not significantly different when comparing the respective formations. Levodopa pharmacokinetic parameters were the same between the Parkinson's disease patients and healthy subjects, except for levodopa apparent clearance, which was approximately two‐thirds lower in Parkinson's disease patients compared with healthy subjects for both levodopa/decarboxylase inhibitor combinations, which might result in higher levodopa area under the curve in patients with Parkinson's disease than in healthy volunteers. Conclusion Levodopa pharmacokinetics differ after administration of levodopa/benserazide and levodopa/carbidopa. This information cold be useful for adjustment of medication in Parkinson's disease patients, especially with motor complications.

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Effect of Clarithromycin on the Pharmacokinetics of Cabergoline in Healthy Controls and in Patients With Parkinson’s Disease

Cited by 22 publications

References 25 publications

Cabergoline: a review of its use in the inhibition of lactation for women living with HIV

Cabergoline: a review of its use in the inhibition of lactation for women living with HIV

Pharmacokinetic Drug Interactions of Antimicrobial Drugs: A Systematic Review on Oxazolidinones, Rifamycines, Macrolides, Fluoroquinolones, and Beta-Lactams

Pharmacokinetics of levodopa/benserazide versus levodopa/carbidopa in healthy subjects and patients with Parkinson's disease

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