Testing Of Drug Interactions Research Articles

Impact of Definitive Drug-Drug Interaction Testing on Medication Management and Patient Care.

Background and ObjectiveAegis Sciences Corporation developed a test (InterACT Rx™) that objectively and definitively identifies substances known to interact with drug–drug interaction-prone medications commonly prescribed in the treatment of chronic pain and behavioral health disorders. The objective of this study was to assess the severity of identified drug–drug interactions, the reduction in the frequency and severity of identified drug–drug interactions, and the impact of the test on healthcare utilization.MethodsPatients with chronic pain, behavioral health disorders, or both who had one or more drug–drug interaction tests and one or more drug–drug interactions identified in the study period were included. Drug–drug interaction test results described the number and severity of interactions and detected substances involved in drug–drug interactions. Patients’ electronic medical records were obtained to analyze outpatient visits and prescription medications. The cost of outpatient visits was based on the Medicare Physician Fee Schedule. Outcomes were compared between the pre- and post-study index periods to determine the impact of the drug–drug interaction test on patient care.ResultsA total of 262 patients were included. The majority of drug–drug interactions detected (77.9%) at index were of moderate severity. The number of monthly all-cause and pain-related outpatient visits was reduced in the post-index period compared with the pre-index period (0.74–0.54 and 0.69–0.49, respectively). Associated costs were reduced from US$64.92 to US$51.20, and from US$62.42 to US$47.62, (p < 0.0001 for both) for all-cause and pain-related outpatient visits, respectively. Follow-up drug–drug interaction testing for 43 patients revealed that previously reported drug–drug interactions at the index test were no longer identified in the subsequent test for 39.5% of patients.ConclusionsEmploying a definitive test to detect substances whose interactions may cause adverse drug events can enhance a provider’s insights, drive clinical decision making, and improve patient outcomes.Electronic supplementary materialThe online version of this article (10.1007/s40801-018-0143-z) contains supplementary material, which is available to authorized users.

Drug interaction test reduces outpatient visits and costs

Drug interaction test reduces outpatient visits and costs

Drug interaction test reduces outpatient visits and costs

Drug interaction test reduces outpatient visits and costs

Effects of Herbal Mixture Extract on Menopausal Hot Flashes and Pharmacokinetics in Ovariectomized Rat Models

This study was conducted to evaluate the effects of Cynanchum wilfordii Hemsley, Phlomis umbrosa Turcz., and Angelica gigas Nakai extract (CPAE) on the reduction of tail skin temperature (TST) in ovariectomized (OVX) rats. To evaluate TST reduction in ovariectomized rats, 125, 250, and 1000 mg/kg CPAE was administered to rats for 1 week. The measurement of TST after the induction of artificial stress revealed a significant temperature reduction effect in the CPAE administration group (ppp<0.01). In addition, in a drug interaction test between tamoxifen, an anti-estrogen drug, and CPAE, no significant difference was found between the pharmacokinetic (PK) profiles after the administration of tamoxifen only and the combination of tamoxifen and CPAE. We also found that CPAE did not affect CYP2d4 and CYP3a2, which affect tamoxifen metabolism, in a subsequent experiment on liver tissues extracted during the drug interaction test. In this study, we found that CPAE inhibited temperature increase on the tail skin of OVX rats, and therefore is effective in the improvement of hot flashes. CPAE may be potentially used for the improvement of hot flashes induced by the administration of tamoxifen.

Nanostructured SERS-electrochemical biosensors for testing of anticancer drug interactions with DNA

Widely used anti-cancer treatments involving chemotherapeutic drugs result in cancer cell damage due to their strong interaction with DNA. In this work, we have developed laboratory biosensors for screening chemotherapeutic drugs and to aid in the assessment of DNA modification/damage caused by these drugs. The sensors utilize surface-enhanced Raman scattering (SERS) spectroscopy and electrochemical methods to monitor sensory film modification and observe the drug-DNA reactivity. The self-assembled monolayer protected gold-disk electrode (AuDE) was coated with a reduced graphene oxide (rGO), decorated with plasmonic gold-coated Fe2Ni@Au magnetic nanoparticles functionalized with double-stranded DNA (dsDNA), a sequence of the breast cancer gene BRCA1. The nanobiosensors AuDE/SAM/rGO/Fe2Ni@Au/dsDNA were then subjected to the action of a model chemotherapeutic drug, doxorubicin (DOX), to assess the DNA modification and its dose dependence. The designed novel nanobiosensors offer SERS/electrochemical transduction, enabling chemically specific and highly sensitive analytical signals generation. The SERS measurements have corroborated the DOX intercalation into the DNA duplex whereas the electrochemical scans have indicated that the DNA modification by DOX proceeds in a concentration dependent manner, with limit of detection LOD=8µg/mL (S/N=3), with semilog linearity over 3 orders of magnitude. These new biosensors are sensitive to agents that interact with DNA and facilitate the analysis of functional groups for determination of the binding mode. The proposed nanobiosensors can be applied in the first stage of the drug development for testing the interactions of new drugs with DNA before the drug efficacy can be assessed in more expensive testing in vitro and in vivo.

Drug interactions with rifampicin: well known but not considered?

ObjectivesEnquiries to the drug information centre revealed that clinicians were not aware of the importance of rifampicin drug interactions. We conducted a short time study to demonstrate the relevance of...

Immuno‐virological discordance is associated with a higher frequency of AIDS, severe non‐AIDS, and death

Persistent immunosuppression despite viral suppression (immunovirological discordance, ID) has been associated with higher risk of AIDS and death, although the risk for AIDS seems to decrease with longer time of suppressed viral load (sVL). The impact of ID on a composite endpoint of AIDS/serious non‐AIDS/death has not been thoroughly investigated. Patients in EuroSIDA starting ≥1 new antiretroviral drugs after January 2001, when CD4 was &lt;200 cells/mm3 and VL &gt;500 copies/mL, and who achieved a sVL ≤50 copies/mL within 1 year were included. Person‐years of follow‐up (PYFU) accrued from the date of sVL until the first of a new AIDS or severe non‐AIDS (SNA) event or death, viral rebound &gt;50 copies/mL (first of 2 consecutive values) or last visit. Rate ratios (RR) were calculated using Poisson regression according to whether or not patient's current CD4 count was still below 200 cells/mm3 (ID). Models were stratified according to whether or not persons were ART‐naïve at baseline. Multivariable models included age, HBV/HCV status, mode of HIV transmission, race, cohort, anemia, diabetes, hypertension or current eGFR, current cART, number of previous antiretrovirals, and time to viral suppression. 994 patients satisfied the inclusion criteria and contributed 4520 PYFU. Median age was 41 (IQR 34–47) years and 72.8% were male. 36.5% of patients were ART‐naïve and started a median of 3 (IQR 2–3) new drugs. 31 AIDS and 58 non‐AIDS events occurred, and 31 patients died (7 due to AIDS, 24 due to SNA). The rate of the combined endpoint in patients with ID (50.3 per 1000 PYFU [95% CI 35.2–69.9]) was higher than in patients recovered from ID (22.1 [17.6–27.3], adjusted RR 2.08 [1.32–3.28]; table). This was similar regardless of whether or not people were ART‐naïve before starting a new drug (interaction test p=0.47). In ID, rate was highest in the first 6 months of sVL (63.1 [33.6–107.9]) and declined thereafter (month 6–12: 60.5 [26.1–119.2],&gt;12 months: 39.8 [22.2–65.6], adjusted RR compared to month 0–6 0.52 [0.24–1.13]). In analyses with endpoints AIDS/death due to AIDS and SNA/death due to SNA separately, the adjusted RR of ID vs. non ID was 4.11 ([1.76–9.60]; p=0.001) and 1.46 ([0.81–2.61]; p=0.207), respectively. Exposure No.events PYFU Rate (95%CI) Crude RR (95%CI) Adjusted**RR (95%CI) All patients No Discordance 84 3805 22.1 (17.6–27.3) 1 1 Discordance 36 716 50.3 (35.2–69.6) 2.28 (1.54–3.38) 2.08 (1.32–3.28) ART‐naïve* patients No Discordance 29 1324 21.9 (14.7–31.5) 1 1 Discordance 9 228 39.5 (18.1–74.9) 1.80 (0.84–3.85) 1.87 (0.81–4.33) ART‐treated* patients No Discordance 55 2481 22.2 (16.7–28.9) 1 1 Discordance 27 488 55.4 (36.5–80.6) 2.50 (1.67–3.97) 1.89 (1.08–3.32) before starting a new antiretroviral drug according to the inclusion criteria, p(test for interaction):0.47 adjusted for smoking, HBV/HCV coinfection, transmission risk, race, cohort, current cART, change of ART before viral suppression, time to viral suppression, presence of diabetes, hypertension, anemia, current eGFR &lt;90, CD4 nadir, CD4 count and viral load at baseline. ID is a risk factor for clinical disease progression particularly related to AIDS events. In patients with ID, we found a trend for a declining incidence of events with longer periods of sVL, suggesting that sustained viral suppression might be of benefit.

Application and review of the separate ray model to investigate interaction effects

In this paper we review the application of the Separate Ray Model to analyze drug combination experiments coming from a fixed ratio design. The idea is the joint fit of separate concentration response curves to each ray under investigation leading to an interaction index for each together with a 95 percent Confidence Interval. The approach is a simple and easy to implement parametric modeling approach and allows estimation and testing of drug interactions based on regularly sampling in the entire space of all combinations going from pure compound A to pure compound B. The analysis is implemented using the SAS/STAT procedure NLMIXED. Two datasets were provided for the modeling exercise. One included different qualitative effects with some rays showing synergy, others antagonism and again others additivity. The second dataset involved the presence of very large synergy together with different observed background effects for the individual rays. The Separate Ray Model is able to handle these practical issues making it a flexible tool to investigate drug interaction experiments using a fixed ratio design.

Perceptual masking of the chlordiazepoxide discriminative cue by both caffeine and buspirone

Twelve male Sprague-Dawley rats were traitrained to discriminate between the interoceptive stimulus attributes of 5 mg/kg chlordiazepoxide (CDP) and saline in a two-lever operant task under a fixed-ratio 10 (FR-10) schedule of food reinforcement. Caffeine, buspirone, and Ro 15-1788 failed to engender complete generalization when tested in combination with saline. In drug interaction test sessions caffeine (56 mg/kg) blocked the discriminative stimulus properties of the training dose of CDP and shifted the CDP discriminative dose-response function to the right. This rightward shift in CDP discriminative function was paralleled by a concomitant downward shift in the rate-of-responding dose-response function. Drug interaction test sessions conducted with 3.2 mg/kg of buspirone in combination with various doses of CDP engendered a downward shift in both the discriminative and rate-of-responding dose-response functions. Because 3.2 mg/kg buspirone in combination with the training dose of CDP resulted in complete response rate suppression, additional combination tests were conducted with 3 mg/kg CDP, a dose which reliably engendered >90% CDP-appropriate responding, and various doses of buspirone. Similar to the CDP-caffeine interactions, buspirone blocked the cueing properties of 3 mg/kg CDP with a parallel reduction in response rates. Interaction test sessions conducted with Ro 15-1788 and CDP resulted in rightward shifts in both the discriminative and rate functions of CDP. We suggest that the interactions between CDP and both caffeine and buspirone resulted from the perceptual masking of the interoceptive (subjective) effects of CDP, whereas the interaction between Ro 15-1788 and CDP reflect pharmacological antagonism.

Effects of prior saline-morphine discrimination by pigeons on three-way discrimination including two morphine doses

The discriminative stimulus properties of morphine sulfate (MS) and their alteration by naltrexone (NTX) and d-amphetamine (AMP) challenges were examined in a quantitative dose 1, dose 2, and saline (SAL) drug discrimination task utilizing 1.8 mg/kg MS, 10 mg/kg MS, and SAL as discriminative stimuli under a fixed-ratio 30 schedule of food-maintained behavior in two groups of White Carneaux pigeons. Group A (Gp A) (n = 6) subjects (Ss) were initially experimentally- and drug-naive, whereas group B Ss (n = 4) were originally trained in a two-choice MS versus SAL discrimination task, and had a long behavioral and drug history. Significant differences were found in (1) number of sessions to criterion (STC) (group B greater than group A); (2) group A Ss generalized both NTX and AMP to SAL, whereas group B Ss generalized AMP to the low dose (1.8 mg/kg) MS stimulus; and (3) in drug interaction test sessions, the high dose MS stimulus (10 mg/kg) in group A was unmodified by a range of challenge AMP doses (0.32 to 3.2 mg/kg). In contrast, group B Ss exhibited a shift to the low dose or SAL-appropriate keys when the same high dose MS stimulus was challenged by moderate doses of AMP. Group A and group B were similar in their pattern and distribution of responses when tested with various doses of MS, and also when challenge tests of the high dose MS stimulus were made with NTX.(ABSTRACT TRUNCATED AT 250 WORDS)