Tenofovir plasma trough concentrations in people with HIV treated with doravirine versus other antiretroviral regimens

Objective Rituximab (RTX) is effective in induction and maintenance of remission in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). However, uncertainty remains regarding the optimal maintenance dosing regimen. This work evaluates the relationship between variability in RTX dosing and pharmacological response in AAV. Methods A prospective cohort of AAV patients (n=28) with either GPA (n=23) or MPA (n=5) receiving maintenance RTX therapy were followed in a single tertiary care academic medical center over a 2-year period. Patient demographics, RTX dosing information, and trough plasma RTX levels were collected along with laboratory measures of pharmacologic response, including B-cell counts and ANCA titers. Results RTX dosing information from 94 infusions with 59 trough samples were collected with a mean±SD dose of 640±221 mg, dosing interval of 210±88 days, and trough plasma RTX concentration of 622±548 ng/mL. RTX trough concentrations were associated with RTX dose (ρ=0.60, p<0.0001) and dosing interval (ρ=-0.55, p<0.0001). RTX dosing intensity (mg/d) was associated with RTX trough concentrations (ρ=0.57, p<0.0001). Higher dosing intensities were associated with undetectable B-cell repopulation (p<0.0001), but not negative ANCA titers (p=0.6). Stratification of dosing intensities based on the standard dosing regimen of 500 mg every six months (2.4 to 3.3 mg/d) demonstrated that this regimen was associated with B-cell repopulation in 8 of 17 doses (47%) compared to 0 of 23 doses (0%) with the high-dose regimen (>3.3 mg/d) (p<0.0001). Conclusion RTX maintenance dosing of 500 mg every six months may be inadequate to maintain B-cell depletion in the treatment of AAV.

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Pharmacokinetic profile of ABELCET (amphotericin B lipid complex injection): combined experience from phase I and phase II studies.

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.41.10.2201 ◽

1997 ◽

Vol 41 (10) ◽

pp. 2201-2208 ◽

Cited By ~ 60

Author(s):

A Adedoyin ◽

J F Bernardo ◽

C E Swenson ◽

L E Bolsack ◽

G Horwith ◽

...

Keyword(s):

Amphotericin B ◽

Interindividual Variability ◽

Pharmacokinetic Profile ◽

Volume Of Distribution ◽

Lipid Complex ◽

Phase Ii Studies ◽

Amphotericin B Lipid Complex ◽

Trough Concentrations ◽

Dose Limiting Toxicity ◽

Wide Interindividual Variability

Amphotericin B (AmB) has been the most effective systemic antifungal agent, but its use is limited by the dose-limiting toxicity of the conventional micellar dispersion formulation (Fungizone). New formulations with better and improved safety profiles are being developed and include ABELCET (formerly ABLC), but their dispositions have not been well characterized; hence, the reason for their improved profiles remains unclear. This report details the pharmacokinetics of ABELCET examined in various pharmacokinetic and efficacy studies by using whole-blood measurements of AmB concentration performed by high-pressure liquid chromatography. The data indicated that the disposition of AmB after administration of ABELCET is different from that after administration of Fungizone, with a faster clearance and a larger volume of distribution. It exhibits complex and nonlinear pharmacokinetics with wide interindividual variability, extensive distribution, and low clearance. The pharmacokinetics were unusual. Clearance and volume of distribution were increased with dose, peak and trough concentrations after multiple dosings increased less than proportionately with dose, steady state appeared to have been attained in 2 to 3 days, despite an estimated half-life of up to 5 days, and there was no evidence of significant accumulation in the blood. The data are internally consistent, even though they were gathered under different conditions and circumstances. The pharmacokinetics of ABELCET suggest that lower concentrations in blood due to higher clearance and greater distribution may be responsible for its improved toxicity profile compared to those of conventional formulations.

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Intraindividual and Interindividual Variability of Olanzapine Trough Concentrations in Patients Treated With the Long-Acting Injectable Formulation

Journal of Clinical Psychopharmacology ◽

10.1097/jcp.0000000000000913 ◽

2018 ◽

Vol 38 (4) ◽

pp. 365-369 ◽

Cited By ~ 5

Author(s):

Sara Baldelli ◽

Massimo C. Mauri ◽

Chiara Di Pace ◽

Silvia Paletta ◽

Alessandra Reggiori ◽

...

Keyword(s):

Interindividual Variability ◽

Injectable Formulation ◽

Trough Concentrations ◽

Long Acting

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Evaluation of the Safety of a Vancomycin Nomogram Used to Achieve Target Trough Concentrations

Hospital Pharmacy ◽

10.1310/hpj5010-900 ◽

2015 ◽

Vol 50 (10) ◽

pp. 900-910

Author(s):

Kristen A. O'Brien ◽

Steve Mok

Keyword(s):

Trough Concentrations

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Improvement in Attaining Tacrolimus Trough Concentrations via the Implementation of a Strict Weight-Based Dosing Guideline Following Heart Transplantation

Journal of Cardiac Failure ◽

10.1016/j.cardfail.2019.07.189 ◽

2019 ◽

Vol 25 (8) ◽

pp. S66

Author(s):

Lynne Sylvia ◽

Johannes Oster ◽

Amanda Vest ◽

David DeNofrio

Keyword(s):

Heart Transplantation ◽

Trough Concentrations

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Recurrent Methicillin-Resistant Staphylococcus Aureus Osteomyelitis: Combination Antibiotic Therapy with Evaluation by Serum Bactericidal Titers

Annals of Pharmacotherapy ◽

10.1177/106002809502907-807 ◽

1995 ◽

Vol 29 (7-8) ◽

pp. 694-697 ◽

Cited By ~ 9

Author(s):

Sherrie L Aspinall ◽

David M Friedland ◽

Victor L Yu ◽

John D Rihs ◽

Robert R Muder

Keyword(s):

Staphylococcus Aureus ◽

Back Pain ◽

Antibiotic Therapy ◽

Sedimentation Rate ◽

Methicillin Resistant Staphylococcus Aureus ◽

Blood Cultures ◽

Low Back ◽

Methicillin Resistant ◽

Trough Concentrations

Objective: To report on a patient with recurrent methicillin-resistant Staphylococcus aureus (MRSA) osteomyelitis and bacteremia successfully treated with combination antibiotic therapy. Case Summary: Two sets of blood cultures from a 55-year-old man with fever, malaise, and low back pain grew MRSA. Radiologic studies of the spine showed bony changes consistent with osteomyelitis. Soon after completing 6 weeks of vancomycin, the patient experienced a recurrence of back pain. Laboratory values included an increase in the sedimentation rate to 53 mm/h and positive blood cultures for MRSA. Vancomycin, gentamicin, and rifampin were administered for 8 weeks. Serum inhibitory and bactericidal titers were more than 1:1024 for both the peak and trough concentrations. Radiologic studies of the spine showed healing osteomyelitis. Two years after completion of antibiotic therapy, the infection has not recurred. Discussion: Antibiotic therapy alone was attempted because the patient was considered a risky surgical candidate. Serum inhibitory and bactericidal titers documented the high in vivo activity of the vancomycin, gentamicin, and rifampin combination. Initiation of vancomycin therapy led to disappearance of the fever and back pain. Cure was documented by sustained normalization of the erythrocyte sedimentation rate and radiologic evidence of healing. Conclusions: Combination antibiotic therapy with vancomycin, rifampin, and low-dose gentamicin (1 mg/kg q12h) may be useful for deep-seated tissue infection caused by MRSA.

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