Chronopharmacokinetics of doxorubicin in patients with breast cancer

Canal, Pierre; Sqalli, A; Forni, M; Chevreau, Christine; Pujol, André; Bugat, R.; Roché, H.; Oustrin, J; Houin, Georges

doi:10.1007/bf00315211

Cited by 26 publications

(9 citation statements)

References 11 publications

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“…Circadian timing significantly influences the plasma and/or urinary pharmacokinetics of intravenously administered 5-fluorouracil, methotrexate, doxorubicin, epirubicin, and cisplatin in cancer patients (125)(126)(127)(128)(129)(130). This is also the case for orally administered busulfan, 6-mercaptopurine, and tegafur/uracil (120,(131)(132)(133)(134).…”

Section: Spontaneous or Imposed Circadian Control Of Anticancer Drug mentioning

confidence: 92%

Circadian Timing in Cancer Treatments

Lévi

Okyar

Dulong

et al. 2010

Annu. Rev. Pharmacol. Toxicol.

394

421

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The circadian timing system is composed of molecular clocks, which drive 24-h changes in xenobiotic metabolism and detoxification, cell cycle events, DNA repair, apoptosis, and angiogenesis. The cellular circadian clocks are coordinated by endogenous physiological rhythms, so that they tick in synchrony in the host tissues that can be damaged by anticancer agents. As a result, circadian timing can modify 2- to 10-fold the tolerability of anticancer medications in experimental models and in cancer patients. Improved efficacy is also seen when drugs are given near their respective times of best tolerability, due to (a) inherently poor circadian entrainment of tumors and (b) persistent circadian entrainment of healthy tissues. Conversely, host clocks are disrupted whenever anticancer drugs are administered at their most toxic time. On the other hand, circadian disruption accelerates experimental and clinical cancer processes. Gender, circadian physiology, clock genes, and cell cycle critically affect outcome on cancer chronotherapeutics. Mathematical and systems biology approaches currently develop and integrate theoretical, experimental, and technological tools in order to further optimize and personalize the circadian administration of cancer treatments.

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Section: Spontaneous or Imposed Circadian Control Of Anticancer Drug mentioning

confidence: 92%

Circadian Timing in Cancer Treatments

Lévi

Okyar

Dulong

et al. 2010

Annu. Rev. Pharmacol. Toxicol.

394

421

View full text Add to dashboard Cite

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“…A circadian phase dependency has also been reported for the pharmacokinetics of other protease inhibitors, as well as other widely used drugs (e.g. digoxin, doxorubicin, gentamicin, nifedipine) [6–10].…”

Section: Introductionmentioning

confidence: 99%

Absence of circadian variation in the pharmacokinetics of lopinavir/ritonavir given as a once daily dosing regimen in HIV‐1‐infected patients

Heeswijk

Bourbeau²,

Seguin

et al. 2005

Brit J Clinical Pharma

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AimsTo compare the pharmacokinetics of lopinavir/ritonavir (LPV/r) 800/200 mg administered once daily in the morning compared with the evening. MethodsThis was a randomized, two-way, cross-over study in HIV + subjects. In each subject the pharmacokinetics of each drug were characterized after 2 weeks of LPV/r 800/ 200 mg administered once daily at 08.00 h and 19.00 h. On study days, LPV/r was taken with a standardized meal (800 kCal, 25% from fat) after fasting for at least 5 h. LPV/r concentrations were measured by LC-MS/MS, and the data were analyzed by noncompartmental pharmacokinetic analysis. ResultsFourteen subjects completed the study (all men, mean age/weight 44 year/81 kg). The median (interquartile range) LPV AUC(0,24 h), maximum plasma concentration ( C max ) and concentration at the end of the dosing interval ( C 24 h ) after am and pm dosing was, respectively, 143 (116-214) mg l -1 h, 12.8 (10.3-17.2) mg l -1 , 1.34 (0.58-3.25) mg l -1 , and 171 (120-232) mg l -1 h, 12.9 (8.22-16.3) mg l -1 , 1.15 (0.59-1.98) mg l -1 . The geometric mean ratio (GMR, am : pm) and 95% CI of the LPV AUC(0,24 h), C max , and C 24 h was 0.91 (0.79, 1.06), 1.11 (0.94, 1.32), and 1.19 (0.72, 1.96), respectively. The median ritonavir C max after am and pm dosing was 1.05 and 0.90 mg l -1 , respectively. The GMR (95% CI) of the RTV AUC(0,24 h), C max , and C 24 h was 0.93 (0.80, 1.08), 1.27 (1.00, 1.63), and 1.04 (0.68, 1.60), respectively. Administration of LPV/r in a once-daily regimen was generally well tolerated. ConclusionsNo differences were observed in the pharmacokinetics of LPV/r after am or pm dosing with food, which suggests that this once daily combination, can be taken in the morning or evening. Such flexibility in dosing may improve adherence.

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“…2). In addition, many researchers suggested that the pharmacokinetics of anti-cancer drugs, doxorubicin and tamoxifen, exhibit circadian variations [35,36]. In this study, sensitivity to doxorubicin and tamoxifen also increased upon co-treatment of KS15 ( Fig.…”

Section: Discussionmentioning

confidence: 78%