Lopinavir/ritonavir reduces lamotrigine plasma concentrations in healthy subjects

Lee, Manon J. van der; Dawood, Lara; Hofstede, H.J.M. ter; Graaff-Teulen, Marga J. A. de; Kolmer, E.W.J. van Ewijk-Beneken; Caliskan‐Yassen, Nurcan; Koopmans, P.P.; Burger, David M.

doi:10.1016/j.clpt.2006.04.014

Cited by 83 publications

(46 citation statements)

References 26 publications

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“…Drug-drug interactions in HIVassociated pain management are not restricted only to opioids; concomitant administration of lopinavir/ritonavir caused a 46% reduction in the plasma concentrations of lamotrigine, which is an antiepileptic recommended as second or third line drug for the treatment of neuropathic pain [6]. The mechanism behind this interaction might be the induction in lamotrigine glucuronidation [48]. Theoretically, the induction of glucuronidation could have an influence on the metabolism of oxycodone and its metabolites, but these metabolic routes are of minor importance [49] and they were not investigated in this study.…”

Section: Discussionmentioning

confidence: 99%

Oxycodone concentrations are greatly increased by the concomitant use of ritonavir or lopinavir/ritonavir

Nieminen

Hagelberg

Saari

et al. 2010

Eur J Clin Pharmacol

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To cite this version:Methods: A randomized crossover study design with 3 phases at intervals of 4 weeks was conducted in 12 healthy volunteers. Ritonavir 300 mg, lopinavir/ritonavir 400/100 mg or placebo b.i.d. for 4 days was given to the subjects. On day 3, 10 mg oxycodone hydrochloride was administered orally. Plasma concentrations of oxycodone, noroxycodone, oxymorphone and noroxymorphone were determined for 48 h. Pharmacokinetic parameters were calculated with standard noncompartmental methods. Behavioural effects and experimental cold pain analgesia were assessed for 12 h. ANOVA for repeated measures was used for statistical analysis.Results: Ritonavir and lopinavir/ritonavir increased the area under the plasma concentration-time curve of oral oxycodone by 3.0-(range 1.9-to 4.3-fold; P<0.001) and 2.6-fold (range 1.9-to 3.3-fold; P<0.001). The mean (± SD) elimination half-life prolonged after ritonavir and lopinavir/ritonavir from 3.6 ± 0.6 to 5.6 ± 0.9 h (P<0.001) and 5.7 ± 0.9 h (P<0.001), respectively. Both ritonavir (P<0.001) and lopinavir/ritonavir (P<0.05) increased the self-reported drug effect of oxycodone. Conclusions:Ritonavir and lopinavir/ritonavir greatly increase the plasma concentrations of oral oxycodone in healthy volunteers and enhance its effect. When oxycodone is used clinically in patients during ritonavir and lopinavir/ritonavir treatment, reductions in oxycodone dose may be needed to avoid opioid-related adverse-effects.

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Section: Discussionmentioning

confidence: 99%

Oxycodone concentrations are greatly increased by the concomitant use of ritonavir or lopinavir/ritonavir

Nieminen

Hagelberg

Saari

et al. 2010

Eur J Clin Pharmacol

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“…In addition to inhibition, interactions with glucuronidation can occur through induction of UGT enzymes. Studies have reported that rifampicin and lopinavir/ritonavir induced lamotrigine glucuronidation, which required a doubling of the dose to maintain a therapeutic plasma concentration [34,35]. These examples show that drug-drug interactions through modulation of glucuronidation can be clinically significant.…”

Section: Glucuronidation As a Pathway For Drug Interactionsmentioning

confidence: 99%

Effects of Herbal Supplements on Drug Glucuronidation. Review of Clinical, Animal, andIn VitroStudies

Mohamed

Frye

2010

Planta Med

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“…80 However, the antiretroviral drugs lopinavir and ritonavir decrease lamotrigine plasma levels. 81 Carbamazepine is an inducer of CYP3A enzymes and may increase the metabolism of the antiretroviral drugs indinavir and delavirdine. 47 On the other hand, ritonavir may raise the serum levels of carbamazepine.…”

Section: Maniamentioning

confidence: 99%

HIV infection and psychiatric illness

Owe‐Larsson

Säll²,

Salamon³

et al. 2009

Afr. J. Psych

139

125

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Introduction HIV is a ribonucleic acid (RNA) retrovirus that is the causative agent for AIDS. HIV belongs to the Lentivirus genus in the family Retroviridae, characterized by a replication cycle in which the viral RNA is reverse transcribed into a DNA proviral form that is integrated into the host cell genome. The retrovirus is composed of two copies of single-stranded RNA that codes for the virus's 9 genes. The RNA is non-covalently linked to the core proteins, which in turn is surrounded by a viral envelope, which enables the virus to enter cells by binding to a specific cellular receptor located on the surface of cluster of differentiation 4 (CD4) cells. 1 A few years after the discovery of HIV-1, a second virus, HIV-2, was found in West Africa. HIV-1 and HIV-2 differ regarding their content of the genome, resulting in lower AIDS rates in HIV-2 infected individuals. 2 Once exposed to the body, the HIV virus antibodies may be detected after an acute flu-like illness, and then proceeds to infect specific cells of the immune system during an asymptomatic period that may last for years. In order to enter a cell, HIV must bind to CD4, typically found on T lymphocytes, blood monocytes, macrophages and some dendrite cells, and subsequently to one or a combination of several possible chemokine co-receptors, usually CCR5 and CXCR4. 3,4 The late HIV infection and psychiatric illness B Owe-Larsson, L Säll, E Salamon, C Allgulander Karolinska Institutet, Department of Clinical Neuroscience, Section of Psychiatry at Karolinska University Hospital Huddinge, Stockholm, Sweden Abstract Objective: To review the clinical features and current knowledge on the treatment of psychiatric symptoms and disorders in patients with human immunodeficiency virus (HIV) infection. Method: We searched the PubMed database combining HIV/AIDS with different keywords for psychiatric diagnoses and symptoms (e.g. depression, mania, anxiety, psychosis, dementia, substance abuse) and for psychopharmacological treatment. The years covered by these searches included 1980 to 2008. Results: Patients with HIV infection are at an increased risk of psychiatric illness. Major depressive disorder and subsyndromal depressive symptoms, as well as anxiety disorder and substance abuse are more prevalent among HIV infected individuals than among the general population. HIV-associated neurocognitive disorders (HAND) are common among HIV patients, and HIV-associated dementia (HAD) is a serious condition during the acquired immune deficiency syndrome (AIDS) stage of HIV disease. Secondary mania and psychosis might be the first clinical symptom of HIV dementia. The introduction of highly active anti-retroviral therapy (HAART) has resulted in significant decreases in morbidity and mortality for HIV infected patients. HAART has also decreased the incidence of HAD, but does not give complete protection from this condition. The utility of psychotropic medications in HIV patients has not been studied sufficiently as a basis for guidelines, and more controlled trials are n...

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Lopinavir/ritonavir reduces lamotrigine plasma concentrations in healthy subjects

Cited by 83 publications

References 26 publications

Oxycodone concentrations are greatly increased by the concomitant use of ritonavir or lopinavir/ritonavir

Oxycodone concentrations are greatly increased by the concomitant use of ritonavir or lopinavir/ritonavir

Effects of Herbal Supplements on Drug Glucuronidation. Review of Clinical, Animal, andIn VitroStudies

HIV infection and psychiatric illness

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