Pharmacokinetics and Safety of Caspofungin in Older Infants and Toddlers

ABSTRACT Although information about the efficacy and safety experience with caspofungin at 50 mg/m2 daily is available for children and adolescents, the dosing regimen in infants and toddlers 3 to 24 months of age has yet to be established. We studied the pharmacokinetics and safety of caspofungin at 50 mg/m2 once daily in nine patients 10 to 22 months (median, 13 months) of age with fever and neutropenia who received caspofungin once daily for 2 to 21 (mean, 9.3) days. Plasma caspofungin concentrations were measured by high-performance liquid chromatography assay on days 1 and 4. On day 4, the area under the curve from 0 to 24 h (AUC0-24) was 130.3 μg-h/ml, the peak concentration (C 1) was 17.2 μg/ml, and the trough concentration (C 24) was 1.6 μg/ml. The day 4 geometric mean ratios (GMRs) and 90% confidence interval (CI) for these parameters in infants/toddlers relative to adults were 1.26 (1.06, 1.50), 1.83 (1.57, 2.14), and 0.81 (0.64, 1.04), respectively. Relative to children (2 to 11 years of age), the day 4 GMRs (and 90% CI) were 1.13 (0.89, 1.44), 1.10 (0.85, 1.42), and 1.12 (0.72, 1.76), respectively. The harmonic mean elimination phase t 1/2 in infants/toddlers (8.8 h) was reduced ∼33% relative to adults (13.0 h) but was similar to that in children (8.2 h). Clinical adverse events occurred in seven patients (78%); none were considered drug related. Laboratory adverse events occurred in five patients (56%) and were considered drug related in three (33%). There were no infusion-related events or discontinuations due to toxicity. Caspofungin at 50 mg/m2 daily was well tolerated in infants and toddlers; the AUC and caspofungin C 24 were generally comparable to those in adults receiving caspofungin at 50 mg daily.

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Pharmacokinetics and Safety of Caspofungin in Neonates and Infants Less than 3 Months of Age

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00868-08 ◽

2008 ◽

Vol 53 (3) ◽

pp. 869-875 ◽

Cited By ~ 93

Author(s):

Xavier Sáez-Llorens ◽

Mercedes Macias ◽

Padmanabha Maiya ◽

Juan Pineros ◽

Hasan S. Jafri ◽

...

Keyword(s):

Adverse Events ◽

Plasma Levels ◽

High Performance ◽

Neonatal Intensive Care ◽

Geometric Mean ◽

Safety Data ◽

Serious Adverse Events ◽

Once Daily ◽

Young Infants ◽

Number Of Patients

ABSTRACT Candida infections represent a major threat in neonatal intensive care units. This is the first prospective study to obtain caspofungin plasma levels and safety data for neonates and very young infants. Patients of <3 months of age receiving intravenous amphotericin B for documented or highly suspected candidiasis were enrolled in a single-dose (n = 6) or subsequent multiple-dose (n = 12) panel; all received caspofungin at 25 mg/m2 once daily as a 1-hour infusion. Caspofungin plasma levels were measured by high-performance liquid chromatography and compared to historical data from adults. Patient chronological ages ranged from 1 to 11 weeks, and weights ranged from 0.68 to 3.8 kg. Gestational ages ranged from 24 to 41 weeks. Geometric mean (GM) peak (C 1 h) and trough (C 24 h) caspofungin levels were 8.2 and 1.8 μg/ml, respectively, on day 1, and 11.1 and 2.4 μg/ml, respectively, on day 4. GM ratios for C 1 h and C 24 h for neonates/infants relative to adults receiving caspofungin at 50 mg/day were 1.07 and 1.36, respectively, on day 1, and 1.18 and 1.21, respectively, on day 4. Clinical and laboratory adverse events occurred in 17 (94%) and 8 (44%) patients, respectively. Five patients (28%) had serious adverse events, none of which were considered drug related. Caspofungin at 25 mg/m2 once daily was well tolerated in this group of neonates/infants of <3 months of age and appears to provide relatively similar plasma exposure to that obtained in adults receiving 50 mg/day. However, the small number of patients studied precludes any definitive recommendations about caspofungin dosing for this group comprising a broad range of ages and weights.

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Efficacy and Safety of Deracoxib for the Control of Postoperative Pain and Inflammation Associated with Dental Surgery in Dogs

ISRN Veterinary Science ◽

10.5402/2011/593015 ◽

2011 ◽

Vol 2011 ◽

pp. 1-7 ◽

Cited By ~ 4

Author(s):

Stephen E. Bienhoff ◽

Eric S. Smith ◽

Linda M. Roycroft ◽

Elizabeth S. Roberts ◽

Larry D. Baker

Keyword(s):

Postoperative Pain ◽

Adverse Events ◽

Treatment Response ◽

Pain Scale ◽

Efficacy And Safety ◽

Dental Surgery ◽

Once Daily ◽

To Receive

The efficacy and safety of deracoxib administered at 1-2 mg/kg/day for 3 days was assessed for the control of postoperative pain and inflammation associated with dental surgery in dogs. Client-owned dogs scheduled for dental extractions were premedicated with butorphanol and randomly assigned to receive either deracoxib (n=31) or placebo (n=31) preoperatively and again once daily for 2 additional days. Dogs were evaluated prior to and after surgery using a modified Glasgow Composite Pain Scale (mGCPS). Dogs could be rescued at any time if they scored ≥4 on the mGCPS or in cases of obvious discomfort. Rescued dogs were considered treatment failures for determining treatment response and were removed from the study. Of the 62 dogs enrolled, 57 were usable for the efficacy analyses and all were assessed for safety. Four of 27 deracoxib-treated dogs (14.8%) were rescued compared to 20 of 30 placebo dogs (66.7%) (P=0.0006). Deracoxib-treated dogs also had numerically lower mGCPS scores. Eight of 31 deracoxib dogs (26%) had adverse events reported compared to 6 of 31 placebo dogs (19%). Results indicate perioperative administration of deracoxib to dogs at 1-2 mg/kg/day for 3 days significantly improves analgesia after dental surgery.

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The efficacy and safety of tacrolimus suppositories in patients with localized ulcerative colitis

10.21203/rs.3.rs-50065/v1 ◽

2020 ◽

Author(s):

Shizuma Omote ◽

Tatsuya Toyokawa ◽

Ryohei Sumii ◽

Akira Nakanishi ◽

Yuka Kadowaki ◽

...

Keyword(s):

Ulcerative Colitis ◽

Adverse Events ◽

Blood Concentration ◽

Efficacy And Safety ◽

Monitoring Methods ◽

Once Daily ◽

Mayo Score ◽

Amino Salicylic Acid ◽

One Year ◽

Dose Change

Abstract Background Tacrolimus is a calcineurin inhibitor used for the treatment of 5-Amino-salicylic acid (5-ASA) and systematic corticosteroid refractory ulcerative colitis. However, systemic administration of tacrolimus could lead to many adverse events. Therefore, we used tacrolimus suppositories as a local therapeutic agent and examined its efficacy and safety with strict blood concentration monitoring. Methods Sixteen patients with ulcerative colitis were administered a 0.5-mg tacrolimus suppository once daily. In cases with an insufficient clinical effect, additional amounts, at an increment of 0.5 mg of tacrolimus, were administered. The blood concentration was measured two weeks after the start of treatment or any dose change and every four weeks thereafter. Results The partial Mayo score was 5.31 before the start of treatment, and it decreased significantly after 2 (2.56, P = 0.001), 4 (1.53, P < 0.001), and 8 (1.47, P = < 0.001) weeks of treatment. The median duration of tacrolimus treatment was 24 (range 2–96) weeks, and 6 patients were treated continuously for more than one year after the pMayo score improved. No exacerbation of adverse events during the treatment regimen was observed. The effects and safety of tacrolimus suppositories were verified with strict blood concentration monitoring. Conclusions Our findings suggest that the application of tacrolimus suppositories is safe and effective in the treatment of patients with ulcerative colitis.

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Absence of Effect of Rufloxacin on Theophylline Pharmacokinetics in Steady State

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.42.9.2359 ◽

1998 ◽

Vol 42 (9) ◽

pp. 2359-2364 ◽

Cited By ~ 6

Author(s):

Martina Kinzig-Schippers ◽

Uwe Fuhr ◽

Marina Cesana ◽

Carola Müller ◽

A. Horst Staib ◽

...

Keyword(s):

Steady State ◽

Adverse Events ◽

Compartment Model ◽

Volume Of Distribution ◽

Reversed Phase ◽

Pharmacokinetic Parameters ◽

Time Curve ◽

Elimination Phase ◽

Once Daily ◽

Model Independent

ABSTRACT Several quinolone antibacterial agents are known to inhibit the metabolism of theophylline, with the potential to cause adverse events due to raised theophylline concentrations during coadministration. A randomized crossover study was therefore conducted with 12 healthy male volunteers (ages, 23 to 34 years; body weight, 64 to 101 kg) to evaluate a possible interaction between rufloxacin and theophylline. Both drugs were administered at steady state. Following the administration of an oral loading dose of 400 mg on day 1, rufloxacin was given orally at 200 mg once daily on days 2 to 7 during one period only. During both periods, 146 mg of theophylline was administered orally twice daily for 3 days (which were days 4 to 6 of the rufloxacin coadministration period) and intravenously once the next morning to test for an interaction. Theophylline and rufloxacin concentrations were measured by reversed-phase high-pressure liquid chromatography, the pharmacokinetics of theophylline at steady state following administration of the last dose were calculated by compartment-model-independent methods. To compare the treatments, analysis of variance-based point estimates and 90% confidence intervals (given in parentheses) were calculated for the mean ratios of the pharmacokinetic parameters from the test (rufloxacin coadministration) over those from the reference (theophylline without rufloxacin) period. These were as follows: maximum concentration at steady state, 1.01 (0.96 to 1.07); area under the concentration-time curve from 0 to 12 h, 0.98 (0.94 to 1.02); half-life, 0.99 (0.95 to 1.03); total clearance at steady state, 1.02 (0.99 to 1.06); and volume of distribution in the elimination phase, 1.01 (0.97 to 1.05). In conclusion, rufloxacin did not affect theophylline pharmacokinetics at steady state. Therefore, therapeutic coadministration of rufloxacin and theophylline is not expected to cause an increased incidence of theophylline-related adverse events.

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A randomized, crossover phase I study to assess the effects of formulation and meal consumption on the bioavailability of dovitinib (TKI258).

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.2593 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 2593-2593 ◽

Cited By ~ 1

Author(s):

Sunil Sharma ◽

Ramesh K. Ramanathan ◽

Daniel J. George ◽

Michelle Quinlan ◽

Swarupa Kulkarni ◽

...

Keyword(s):

Kinase Inhibitor ◽

Geometric Mean ◽

Area Under The Curve ◽

Relative Bioavailability ◽

Crossover Designs ◽

Once Daily ◽

Relevant Effect ◽

Crossover Phase ◽

Effect Of Food ◽

To Receive

2593 Background: Dovitinib (TKI258), an oral multitargeted receptor tyrosine kinase inhibitor, is being studied in a phase 3 trial for renal cell carcinoma. A previous study compared the bioavailability of 2 capsule formulations of dovitinib. Arm 1 of the current study compared relative bioavailability of the final market image (FMI) form (monohydrate tablets) with the clinical service form (CSF; anhydrate capsules) of dovitinib. Arm 2 assessed the effect of food on bioavailability of the FMI tablet in adult patients (pts) with advanced solid tumors. Both arms employed crossover designs. Methods: In arm 1, pts were randomized to receive a single 500-mg dose of dovitinib either as a CSF capsule or FMI tablet, followed by a single 500-mg dose of the other formulation after 7 days of rest. Plasma pharmacokinetic (PK) profiles were determined from blood samples. A linear mixed-effects model fitted to log-transformed PK parameters maximal concentration (Cmax) and area under the curve (AUC0-tlast) was used to determine the relative bioavailability of FMI vs CSF. In Arm 2, pts received 300 mg of the FMI formulation once daily for 22 days after being randomized to 1 of 6 meal sequences with 3 fed or nonfed states (no meal [NM], low-fat [LF] meal, or high-fat [HF] meal) on days 8, 15, and 22. The relative bioavailability of dovitinib under LF and HF vs NM state was determined using the same model as arm 1 for the PK parameters Cmax and AUC0-tlast. Results: The study accrued 21 pts to arm 1 and 42 pts to arm 2. Based on the interim analysis, PK was assessed in 17 evaluable pts in arm 1. The geometric mean ratios (GMRs; 90% CI) for Cmax and AUC0-tlast comparing FMI vs CSF were 0.99 (0.91-1.08) and 0.96 (0.89-1.04), respectively. The FMI formulation was used in arm 2; PK was assessed in 19 pts. Cmax GMR (90% CI) was 0.82 (0.71-0.94) and 0.90 (0.78-1.03) for HF/NM and LF/NM, respectively. AUC0-tlastGMR (90% CI) was 0.91 (0.81-1.02) and 0.99 (0.88-1.10) for HF/NM and LF/NM, respectively. Conclusions: The oral bioavailability of the FMI tablet and CSF capsule were comparable, and there was no clinically relevant effect of food (HF or LF meals) on the bioavailability of the FMI tablet form of dovitinib. Clinical trial information: NCT01155713.

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TO EVALUATE EFFICACY AND SAFETY OF RUPATADINE, BILASTINE, AND LEVOCETRIZINE IN ALLERGIC RHINITIS AT TERITARY CARE HOSPITAL, TELANGANA

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2021.v14i12.43427 ◽

2021 ◽

pp. 140-143

Author(s):

NAGUR SHARONE GRACE ◽

SYED ARSHADDUDDIN AHMED ◽

BHUVANESWARI E ◽

SYED HAMZA QUADRI ◽

VEENA B ◽

...

Keyword(s):

Allergic Rhinitis ◽

Adverse Events ◽

Nasal Congestion ◽

Care Hospital ◽

Efficacy And Safety ◽

Open Label ◽

Once Daily ◽

Significant Difference ◽

The Mean ◽

The Government

Objective: Allergic rhinitis (AR) is a heterogeneous disorder characterized by symptoms – sneezing, itching, nasal congestion, and rhinorrhea. The aim of the study is to evaluate the efficacy and safety of rupatadine, bilastine, and levocetirizine in AR. Methods: A prospective, open-label, comparative study was conducted at the Government ENT Hospital, Hyderabad, Telangana. Ninety patients diagnosed with AR were randomized, of whom Group 1 received oral tab. bilastine 20 mg once daily, Group 2 received oral tab. levocetirizine 5 mg once daily, and Group 3 received oral tab. rupatadine with a dose of 10 mg once daily for 2 weeks. The reduction in total nasal symptom score (TNSS) and absolute eosinophil counts (AECs) was compared with baseline and at 2 weeks. Safety was assessed according to adverse events reported during the study period. An analysis of variance was used as a test of significance for the three groups. Results: Overall, 90 cases were included in the study, with 48% of males and 52% of females. All three drugs significantly reduced the TNSS and AEC after treatment compared to before treatment (p<0.05). The mean difference in TNSS and AEC showed no statistically significant difference among the three groups (TNSS: p>0.908 and AEC: p>0.967). In terms of safety, all three drugs showed nearly similar adverse events. Conclusion: In this study, after 2 weeks of follow-up, the three drugs (bilastine, levocetirizine, and rupatadine) showed significant improvement clinically, but the mean reduction in the score of symptoms and AEC was not statistically significant in the treatment of AR.

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Pharmacokinetics of Two Multiple-Dosing Regimens of D0870 in Human Immunodeficiency Virus-Positive Patients: a Phase I Study

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.42.4.903 ◽

1998 ◽

Vol 42 (4) ◽

pp. 903-906 ◽

Cited By ~ 11

Author(s):

S. De Wit ◽

E. O’Doherty ◽

J. Edwards ◽

R. Yates ◽

R. P. Smith ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Adverse Events ◽

Hiv Positive ◽

Loading Dose ◽

Dosing Regimen ◽

Accumulation Ratio ◽

Once Daily ◽

Immunodeficiency Virus ◽

Dosing Regimens ◽

Oral Doses

ABSTRACT D0870 is a triazole with a broad antifungal spectrum, and it has been shown to have both in vitro and in vivo activities against wild-type and fluconazole-resistant strains of Candida albicans. Twenty-two human immunodeficiency virus (HIV)-positive male subjects were enrolled in an open, nonrandomized trial investigating the pharmacokinetics of two different dosing regimens of D0870 and assessing the safety of multiple oral doses of D0870 in HIV-positive subjects and their ability to tolerate multiple oral doses. Nine subjects received an initial loading dose of 50 mg, followed by four once-daily maintenance doses of 10 mg. A further nine subjects received an initial 200-mg loading dose followed by four daily maintenance doses of 25 mg. All subjects were fasting. A single loading dose of 50 mg of D0870 resulted in a mean maximum concentration in serum (C max) of 107 ± 32 ng/ml. Concentrations in plasma were maintained by the 10-mg once-daily dosing regimen as seen by the similar values of the area under the concentration-time curve from 0 to 24 h following dosing on days 1 and 5 and a mean accumulation ratio close to unity (0.90). The terminal plasma half-life of D0870 in plasma following dosing on day 5 ranged from 23 to 85 h (mean, 49 h). A single loading dose of 200 mg of D0870 resulted in a C max of 431 ± 186 ng/ml. Concentrations in plasma were again maintained by the 25-mg daily dosing regimen, with the mean accumulation ratio being close to unity (1.17). The terminal half-life of D0870 in plasma following dosing on day 5 of phase II of the study ranged from 34 to 137 h (mean, 71 h). In addition, the concentrations achieved in the plasma of these HIV-positive subjects were similar to the values predicted from simulations based on data derived from normal, healthy subjects. D0870 was well tolerated. No serious adverse events were experienced during the course of the study, and all volunteers completed the trial. A total of 15 adverse events were reported, but none were considered to be related to the administration of D0870 and all had resolved by the end of the trial. No changes in the hematology, clinical chemistry, or urinalysis parameters were considered to be related to dosing with D0870. No clinically significant changes in the electrocardiogram parameters were noted during the trial. The data generated in this trial support further investigation of these regimens with HIV-positive subjects with fluconazole-susceptible or -resistant oropharyngeal candidosis.

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Review of Efficacy and Safety of Duloxetine 40 to 60 mg Once Daily in Patients with Diabetic Peripheral Neuropathic Pain

Pain Research and Treatment ◽

10.1155/2012/898347 ◽

2012 ◽

Vol 2012 ◽

pp. 1-12 ◽

Cited By ~ 1

Author(s):

Vladimir Skljarevski ◽

Elijah P. Frakes ◽

Doron Sagman ◽

Sarah Lipsius ◽

Alexandra N. Heinloth ◽

...

Keyword(s):

Neuropathic Pain ◽

Adverse Events ◽

Brief Pain Inventory ◽

Primary Outcome Measure ◽

Pain Severity ◽

Efficacy And Safety ◽

Open Label ◽

Double Blind ◽

Peripheral Neuropathic Pain ◽

Once Daily

We summarize efficacy and safety findings from 4 double-blind, placebo-controlled, 12-week studies and 1 open-label, uncontrolled, 34-week maintenance-of-effect (MOE) study that examine duloxetine 40 and 60 mg once daily (QD) in patients with diabetic peripheral neuropathic pain (DPNP). In all placebo-controlled studies, duloxetine showed significantly (P≤.01) greater reduction in pain severity (weekly mean of 24-hour average pain severity ratings, primary outcome measure) compared with placebo. In all placebo-controlled studies, duloxetine showed significantly (P≤.05) greater improvement on brief pain inventory-Interference ratings. Patient global impression of improvement ratings were superior to placebo (P≤.01) for duloxetine patients in all placebo-controlled studies. Response rates (based on 30% pain reduction) ranged from 57% to 68% for duloxetine and from 35% to 47% for placebo and were statistically significantly different (P≤.01) between treatment groups in 3 out of 4 studies. The open-label study showed maintenance of analgesic effect of duloxetine in DPNP. In the duloxetine groups, 4.3% to 14.9% of patients discontinued because of adverse events (placebo groups: 2.6% to 7.4%). Most commonly reported treatment-emergent adverse events were nausea, somnolence, and headache. Duloxetine 40 and 60 mg QD was efficacious and well tolerated in the management of DPNP.

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Doing More With Less: Review of Dolutegravir-Lamivudine, a Novel Single-Tablet Regimen for Antiretroviral-Naïve Adults With HIV-1 Infection

Annals of Pharmacotherapy ◽

10.1177/1060028020933772 ◽

2020 ◽

Vol 54 (12) ◽

pp. 1252-1259

Author(s):

Barbara A. Santevecchi ◽

Stacy Miller ◽

Lindsey M. Childs-Kean

Keyword(s):

Clinical Trials ◽

Adverse Events ◽

Virological Suppression ◽

Phase Iii ◽

Efficacy And Safety ◽

Once Daily ◽

Review Articles ◽

Single Tablet Regimen ◽

Treatment Naïve ◽

Hiv 1

Objective: To review data on efficacy and safety of dolutegravir (DTG) and lamivudine (3TC) in treatment-naïve adults with HIV-1 infection. Data Sources: Phase III clinical trials and review articles were identified through PubMed (1996 to March 2020) and ClinicalTrials.gov (2000 to May 2020) using the keywords dolutegravir, lamivudine, and HIV. Study Selection and Data Extraction: Relevant clinical trials and review articles available in English evaluating efficacy and safety of DTG and 3TC were included. Data Synthesis: The once-daily, single-tablet regimen of DTG/3TC is the first dual antiretroviral therapy (ART) recommended for initial therapy in treatment-naïve adults with HIV-1 infection. DTG and 3TC were compared with a regimen of DTG and tenofovir disoproxil fumarate/emtricitabine in the GEMINI studies and demonstrated noninferiority for the primary end point of virological suppression at up to 96 weeks. No treatment-emergent resistance mutations were identified in a small group of participants who did not reach virological suppression. The regimen is well tolerated, and the most common adverse events reported in trials include headache, diarrhea, nausea, insomnia, and fatigue. Relevance to Patient Care and Clinical Practice: This dual-ART regimen is a favorable treatment option for ART-naïve patients with HIV-1 RNA <500 000 copies/mL, absence of hepatitis B virus, and no resistance to DTG or 3TC. Benefits of dual ART include reduction in treatment-related adverse events and toxicities, drug interactions, and cost. In addition, the once-daily, single-tablet formulation promotes adherence. Conclusions: DTG/3TC has demonstrated efficacy in maintaining virological suppression in ART-naïve patients at up to 96 weeks while minimizing treatment-related adverse events and toxicities.

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Effects of Etravirine Alone and with Ritonavir-Boosted Protease Inhibitors on the Pharmacokinetics of Dolutegravir

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00073-11 ◽

2011 ◽

Vol 55 (7) ◽

pp. 3517-3521 ◽

Cited By ~ 53

Author(s):

Ivy Song ◽

Julie Borland ◽

Sherene Min ◽

Yu Lou ◽

Shuguang Chen ◽

...

Keyword(s):

Plasma Concentration ◽

Protease Inhibitors ◽

Geometric Mean ◽

Area Under The Curve ◽

Integrase Inhibitor ◽

Dosage Interval ◽

Maximum Plasma ◽

Phase 3 ◽

Once Daily ◽

Period 2

ABSTRACTDolutegravir (DTG) is an unboosted, once-daily integrase inhibitor currently in phase 3 trials. Two studies evaluated the effects of etravirine (ETR) alone and in combination with ritonavir (RTV)-boosted protease inhibitors (PIs) on DTG pharmacokinetics (PK) in healthy subjects. DTG 50 mg every 24 h (q24h) was administered alone for 5 days in period 1, followed by combination with ETR at 200 mg q12h for 14 days in period 2 (study 1) or with ETR/lopinavir (LPV)/RTV at 200/400/100 mg q12h or ETR/darunavir (DRV)/RTV at 200/600/100 mg q12h for 14 days in period 2 (study 2). PK samples were collected on day 5 in period 1 and day 14 in period 2. All of the treatments were well tolerated. ETR significantly decreased exposures of DTG, with geometric mean ratios of 0.294 (90% confidence intervals, 0.257 to 0.337) for the area under the curve from time zero until the end of the dosage interval (AUC0-τ), 0.484 (0.433 to 0.542) for the observed maximum plasma concentration (Cmax), and 0.121 (0.093 to 0.157) for the plasma concentration at the end of the dosage interval (Cτ). ETR combined with an RTV-boosted PI affected the exposure of DTG to a lesser degree: ETR/LPV/RTV treatment had no effect on the DTG plasma AUC0-τandCmax, whereas theCτincreased by 28%. ETR/DRV/RTV modestly decreased the plasma DTG AUC0-τ,Cmax, andCτby 25, 12, and 37%, respectively. Such effects of ETR/LPV/RTV and ETR/DRV/RTV are not considered clinically relevant. The combination of DTG and ETR alone should be avoided; however, DTG may be coadministered with ETR without a dosage adjustment if LPV/RTV or DRV/RTV is concurrently administered.

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