C Lindsay Devane

..This review summarizes some of the major pharmacokinetic and pharmacodynamic similarities and differences among these drugs...

..These data do not eliminate the need for caution when prescribing antidepressants with the potential for causing metabolic interactions, but do help allay the fear that such interactions are highly prevalent and routinely hazardous...

..Like other selective serotonin reuptake inhibitors, sertraline is well tolerated in therapeutic dosages and relatively safe in overdosage...

..Psychopharmacology Bulletin...

..Important assumptions in reproductive medicine are that fetal exposure to any medication can present risks in pregnancy--because not all risks are known, as little exposure as possible is desirable...

..The conclusion is drawn that drug interactions from CYP inhibition caused by the newer antidepressants are potentially, but rarely, clinically significant...

..Valproate has an extensive record of use across the lifespan and a good record of tolerability. Some precautions are warranted in its use, but valproate is generally safe whether administered alone or in combination with other therapies...

..Although the connection has not been proven, more stable pharmacokinetic profiles might be the cause for the low occurrence of nausea with some controlled-release newer antidepressants...

..These results demonstrate in vivo that, unlike nefazodone, venlafaxine, sertraline, and fluoxetine do not possess significant metabolic inductive or inhibitory effects on CYP3A4...

..There is a substantial published database supporting safe and effective use of risperidone for treatment of psychosis, agitation, and aggression in elderly patients...

..The newer drugs for treatment of type 2 diabetes are discussed, and considerations are given for avoiding or minimizing drug interactions when prescribing psychoactive drugs to patients with diabetes...

..Adherence to a few guidelines for the design of dosage regimens should limit the effect of drug-drug interactions on patient status and contribute to optimal pharmacotherapy with risperidone...

..Unfortunately, the ideal antidepressant is yet to be formulated. Pharmacologic characteristics for desirable improvements are discussed relative to the currently available drugs...

..Subsequent clinical studies of the plasma concentration versus effect relationships for quetiapine may help to further define guidelines for dosage regimen design...

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..These data suggest a lack of involvement of CYP2D6 in the metabolism of MPH. Drugs that are inhibitors of CYP2D6 when taken concurrently with MPH should not affect its plasma concentration...

..Relevant pharmacologic and pharmacodynamic effects are summarized that support nefazodone as an attractive choice for both the short- and long-term treatment of depression...

..These results document why the rat foetus is particularly susceptible to the pharmacodynamic effects of morphine following maternal administration...

..Furthermore, P-glycoprotein may play a minor role in the transport of d-methylphenidate, d-modafinil, and l-modafinil...

..These conclusions must be weighed in the context of the study's limited assessments and regarded as only the initial investigation into the drug interaction potential of saw palmetto...

..3 +/- 1.8 microM 2 h after DGT treatment. Our results indicate that DGT is unlikely to alter the disposition of medications primarily dependent on the CYP2D6 or CYP3A4 pathways of metabolism...

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..In particular, RSP may interact with its own active metabolite PALI by promoting its brain concentration through inhibiting P-gp-mediated efflux of PALI across endothelial cells of the BBB...

..The multidrug resistance transporter, P-glycoprotein (P-gp), is involved in efflux transport of several antipsychotics in the blood-brain barrier (BBB)...

..St John's wort is a popular herbal product used to treat depression but it has been implicated in drug interactions...

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..Asp260fs, respectively, compared to the wild-type enzyme. These findings indicate that specific CES1 gene variants can lead to clinically significant alterations in pharmacokinetics and drug response of carboxylesterase 1 substrates...

..The mechanisms and consequences of these interactions require further study in humans to establish clinical relevance...

..The homozygous TT genotype for P-gp resulted in an increased AUC of OLZ for SOT administration but not for either condition where sublingual absorption could occur...

..In addition, d-MPH is a relatively weak P-gp substrate, and its entry into the brain may be limited by P-gp. Furthermore, the mechanism by which d-MPH-induced locomotor activity was attenuated in P-gp KO mice remains to be elucidated...

..We hypothesized that olanzapine disposition would be altered as a result of decreased glucuronidation, whereas risperidone disposition would be relatively unaffected...

..7 +/- 4.4 h versus 14.5 +/- 4.3 h). Our results indicate that garlic extracts are unlikely to alter the disposition of coadministered medications primarily dependent on the CYP2D6 or CYP3A4 pathway of metabolism...

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..The objectives of the current study were to quantify placental permeability to antipsychotic medications and to document obstetrical outcomes for women taking these agents proximate to delivery...

..The interindividual variation in expression of P-gp in BBB may represent a source of variation for the access and effects of methadone in the brain...

..In contrast, long-term administration of modafinil significantly decreased systemic exposure to cocaine during the first 180 minutes following intravenous cocaine administration...

..Although the significance of amniotic fluid exposure remains to be determined, these results demonstrate that maternally administered antidepressants are accessible to the fetus in a manner not previously appreciated...

..This review summarizes the current data on drug transporters in the placental passage of medications, with a focus on medications used in clinical psychopharmacology...

..There were no significant differences in the excretion of urinary 8-epi-PGF(2 alpha) after treatment with green tea. We conclude that 14 days of green tea supplementation did not significantly alter in-vivo lipid peroxidation...

..These results indicate that P-gp in the blood-brain barrier significantly influences the brain concentrations of risperidone and 9-OH-risperidone by limiting their CNS access...

..This method is the first HPLC assay with non-MS detection providing sufficient reliability and sensitivity for both pre-clinical and clinical studies of MPH...

..The present results suggest that a potential source of pharmacokinetic interactions exists between BCRP substrates and several antipsychotics...

..Thus, factors influencing P-gp activity within the blood brain barrier in humans may have implications for the therapeutic effects and tolerability of aripiprazole...

..3 ng/mL. The relative standard deviations of intra-day and inter-day variations were < or =8.30% and 7.47%, respectively. This method is rapid, sensitive, and suitable for both basic and clinical studies of atomoxetine...

..Modafinil significantly dampened scores on Visual Analog Scale measures as compared to baseline cocaine conditions. No significant alterations in labs occurred. Further outpatient trials of modafinil appear to be warranted...

..These data define the time course of a persistent effect that fluoxetine, sertraline, and paroxetine have on CYP2D6 following drug discontinuation and should be considered when initiating therapy with a CYP2D6 substrate...

..To compare the rate and extent of absorption of DL-threo-methylphenidate (MPH) from two modified-release MPH formulations at their respective recommended starting doses in healthy adult volunteers...

..These findings indicate that CBD significantly inhibits P-gp-mediated drug transport, suggesting CBD could potentially influence the absorption and disposition of other coadministered compounds that are P-gp substrates...

..These results suggest that P-gp is likely to influence the access to the brain of all of the atypical antipsychotics studied to various degrees. In vivo studies are needed to confirm these findings...

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..However, the present exploratory studies reflect receptor binding affinities only. The specific pharmacological activities (i.e., agonism vs. antagonism) of these compounds await further exploration...

..Clinical implications concerning rational drug selection for an identified or suspected MPH PM are discussed...

..These data suggest that coadministration of inhibitors of CYP3A4 and CYP2C8 may produce clinically significant drug-drug interactions with methadone...

..To determine if a standardized ginkgo supplement significantly alters concentrations of circulating androgenic steroids in humans...

..The validation data support the use of this method for human pharmacokinetic studies of modafinil in patients with known or suspected use of common antidepressants, psychostimulants, and drugs of abuse...

..05). We conclude that quinine as consumed in tonic water does not inhibit CYP2D6 activity in vivo. Thus, quinine should not alter the metabolism of CYP2D6 substrates taken concomitantly with tonic water...

..The observed carrier-mediated nicotine transport in various cell lines may be mediated by other transporter proteins but not P-gp...

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..These results provide functional evidence concordant with prior data for increased brain levels of risperidone following PSC 833 treatment...

..Paroxetine controlled-release is an enteric-coated formulation with release features that may enhance clinical outcome by modifying absorption-related pharmacokinetics, improving tolerability, and maintaining therapeutic benefits..

..This case suggests that atypical antipsychotics, although generally better tolerated than conventional agents, may still result in untoward reactions that may be partially due to individual differences in drug absorption and metabolism...

..Thus, in this study, donepezil did not induce or worsen depressive symptoms in schizophrenic and schizoaffective disorder patients...

..09), and MCP-1 (P=0.02), suggesting that these biomarkers may have become selectively lowered in the serotonergic dose range of venlafaxine. This is the first report of venlafaxine's possible effect on pro-inflammatory biomarkers...

..To determine whether there is a pharmacokinetic drug interaction between quetiapine fumarate and divalproex sodium...

..018, n=13). These results are discussed with respect to other studies using cholinesterase inhibitors as an augmentation strategy in schizophrenia...

..This study will form the basis for subsequent studies which should provide a more rational basis for dosing of methadone in pregnant addicts. ..

..The results of this research will provide support for translational studies in humans to refine treatment guidelines for the use of this class of medications in severely mentally ill patients. ..

..PROJECT NARRATIVE: Autism occurs in approximately 1 in 150 children. The investigators propose a multi-center clinical trial to provide evidence-based guidance in the selection and monitoring of durg treatment of autism. ..