Itraconazole increases but grapefruit juice greatly decreases plasma concentrations of celiprolol

Lilja, Jari J.; Backman, Janne T.; Laitila, Jouko; Luurila, Harri; Neuvonen, Pertti J.

doi:10.1067/mcp.2003.26

Cited by 127 publications

(129 citation statements)

References 30 publications

Supporting

Mentioning

120

Contrasting

Unclassified

Order By: Relevance

“…Levothyroxine is susceptible to complexation with other drugs in the gastrointestinal tract [10,11], and grapefruit juice is characterized by its acidity [7]. Thus, grapefruit juice components appear to have only a minor potential to interfere with the absorption of levothyroxine from the intestinal lumen either by binding to the drug or by increasing the acidity of the gastrointestinal tract.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, it has been shown that grapefruit juice markedly decreases plasma concentrations of fexofenadine and celiprolol [6,7]. It has been suggested that the mechanism of the grapefruit juice-fexofenadine interaction is inhibition of uptake transporters in the intestinal wall that results in decreased absorption [6].…”

Section: Discussionmentioning

confidence: 99%

“…The mechanism of these interactions is mainly inhibition of intestinal CYP3A4 activity, although repeated doses of grapefruit juice may also inhibit the activity of hepatic CYP3A4 [5]. Recently, grapefruit juice has been reported to decrease the plasma concentrations of some drugs, for example fexofenadine [6] and celiprolol [7], possibly by inhibiting intestinal uptake transporters [6].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Effects of grapefruit juice on the absorption of levothyroxine

Lilja¹,

Laitinen

Neuvonen³

2005

Brit J Clinical Pharma

View full text Add to dashboard Cite

AimsOur aim was to study the effect of grapefruit juice on the pharmacokinetics of levothyroxine. MethodsIn a randomized cross-over study with two phases, 10 healthy subjects ingested 200 ml grapefruit juice or water (control) three times daily for 2 days. On day 3, a single 600 m g dose of levothyroxine was administered with 200 ml grapefruit juice or water, which was also ingested 1 h before and 1 h after levothyroxine. Serum concentrations of total thyroxine (T4) and thyroid-stimulating hormone (TSH) were measured up to 24 h. ResultsGrapefruit juice decreased slightly (11%; P < 0.01) the maximal increase of T4 concentration after ingestion of levothyroxine from 66.4 nmol l -1 to 59.4 nmol l -1 (95% CI on the difference -11.3, -2.7). The incremental areas under the serum T4 concentration-time curve (dAUC) during the first 4 and 6 h were also decreased slightly: dAUC(0,4 h) by 13% ( P < 0.05), from 195 nmol l -1 h to 169 nmol l -1 h (95% CI -51, -1) and dAUC(0,6 h) by 9% ( P = 0.085), from 298 nmol l -1 h to 271 nmol l -1 h (95% CI -58, 4). The decrease in the serum concentration of TSH (1.25 mU l -1 ) measured 24 h after ingestion of levothyroxine, was not altered by grapefruit juice. ConclusionsGrapefruit juice may slightly delay the absorption of levothyroxine, but it seems to have only a minor effect on its bioavailability. Accordingly, the clinical relevance of the grapefruit juice-levothyroxine interaction is likely to be small.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Effects of grapefruit juice on the absorption of levothyroxine

Lilja¹,

Laitinen

Neuvonen³

2005

Brit J Clinical Pharma

View full text Add to dashboard Cite

show abstract

“…OATP influences the intestinal absorption of several drugs in clinical use. [10][11][12][13][14] Grapefruit juice decreases the plasma concentrations of some drugs including β-adrenoceptor blocking agents and antihistamines by this mechanism. For example, grapefruit juice was reported to reduce the area under the plasma concentration-time curve (AUC) value for fexofenadine to a mean value of 58% of that when the drug was administered with the corresponding volume of water.…”

Section: )mentioning

confidence: 99%

“…Thus, our goal was to determine the duration of the inhibitory effect of grapefruit juice on OATP by comparison with the duration of the grapefruit juice-mediated effects on CYP3A4 activity. We administered oral celiprolol and midazolam, which are substrates of OATP 3,11) and CYP3A4, 1,14) respectively, on days 1, 3, and 7 (0, 48, and 144 h after the ingestion of grapefruit juice) to healthy subjects. …”

mentioning

confidence: 99%

Comparison of Inhibitory Duration of Grapefruit Juice on Organic Anion-Transporting Polypeptide and Cytochrome P450 3A4

Tanaka

Uchida

Miyakawa

et al. 2013

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Recently, a new type of interaction has been reported in which fruit juices diminish oral drug bioavailability through inhibition of organic anion-transporting polypeptide (OATP). In this study, we aimed to clarify the duration of OATP inhibition by grapefruit juice (GFJ), and to compare it with the duration of GFJ-induced inhibition of cytochrome P450 (CYP) 3A4 activity. Seven healthy volunteers were enrolled in this open-label, single-sequence study. They were orally administered celiprolol (100 mg) and midazolam (15 µg/kg) with water on the control day. Three days later, they ingested GFJ (200 mL) 3 times a day for 3 d. On day 1, the same drugs were administered with GFJ. On days 3 and 7, the same drugs were administered with water. Pharmacokinetics of both drugs were evaluated on each trial day. The peak plasma concentration (C max ) and the area under the plasma concentration-time curve from 0 to 8 h (AUC 0-8 ) of celiprolol significantly decreased on day 1, and the mean ratios of these values and the corresponding control-day values were 0.18 and 0.25, respectively. The C max and AUC 0-8 returned to the control levels on days 3 and 7. In contrast, AUC 0-8 of midazolam were higher on days 1 and 3 than on the control day (mean ratio, 2.12 and 1.47, respectively). The AUC 0-8 returned to the control level on day 7. In conclusion, results of this study indicated that the OATP inhibition caused by GFJ dissipated faster than GFJ-mediated alterations in CYP3A4 activity, which were sustained for at least 48 h.Key words organic anion-transporting polypeptide; cytochrome P450; grapefruit juice Food and medication are often taken together. However, certain foods interact with drugs by altering mechanisms that are important determinants of systemic drug availability. In particular, grapefruit juice is known to alter the pharmacokinetics of over 30 prescription drugs by affecting their bioavailability.1-3) The mechanism of this interaction is inhibition of intestinal cytochrome P450 (CYP) 3A4 activity and increased systemic exposure of CYP3A4 substrates. [4][5][6][7][8] In 2012, the United States Food and Drug Administration issued a press release to warn consumers that the intake of grapefruit juice along with medication could cause dangerous side effects. 9)Recently, a new type of interaction has been reported in which fruit juices diminish oral drug bioavailability through inhibition of the organic anion-transporting polypeptide (OATP) uptake transporter, which is a family of membrane solute carrier (SLC) transporters. OATP influences the intestinal absorption of several drugs in clinical use. [10][11][12][13][14] Grapefruit juice decreases the plasma concentrations of some drugs including β-adrenoceptor blocking agents and antihistamines by this mechanism. For example, grapefruit juice was reported to reduce the area under the plasma concentration-time curve (AUC) value for fexofenadine to a mean value of 58% of that when the drug was administered with the corresponding volume of water.10) Furthermore, celiprolol, ...

show abstract

Introduction to Drug Transporters

Leung¹,

Oganesian²

2008

Drug Metabolism Handbook

View full text Add to dashboard Cite

Itraconazole increases but grapefruit juice greatly decreases plasma concentrations of celiprolol

Cited by 127 publications

References 30 publications

Effects of grapefruit juice on the absorption of levothyroxine

Effects of grapefruit juice on the absorption of levothyroxine

Comparison of Inhibitory Duration of Grapefruit Juice on Organic Anion-Transporting Polypeptide and Cytochrome P450 3A4

Introduction to Drug Transporters

Contact Info

Product

Resources

About