scholarly journals Phase 2b study of 2 dosing regimens of quizartinib monotherapy in FLT3-ITD–mutated, relapsed or refractory AML

Blood ◽  
2018 ◽  
Vol 132 (6) ◽  
pp. 598-607 ◽  
Author(s):  
Jorge E. Cortes ◽  
Martin S. Tallman ◽  
Gary J. Schiller ◽  
Denise Trone ◽  
Guy Gammon ◽  
...  
Keyword(s):  
Risk Profile ◽  
Once Daily ◽  
Bridge To Transplant ◽  
Overall Response ◽  
Key Points ◽  
Daily Dose ◽  
Dosing Regimens ◽  
Refractory Aml

Key Points Quizartinib at 60 mg/day (vs 30 mg/day) was associated with higher overall response, survival, and bridge to transplant. The benefit-risk profile of quizartinib in relapsed or refractory FLT3-ITD–mutated AML warrants further evaluation of 60-mg once-daily dose.

scholarly journals Effect of Oral Gavage Dosing Regimens in Female Tg rasH2 Transgenic Mice

2004 ◽  
Vol 32 (4) ◽  
pp. 413-417 ◽  
Author(s):  
Daniel Morton ◽  
Rani S. Sellers ◽  
Sylvia M. Furst ◽  
Kristen D. Hawley ◽  
Jeffrey R. May
Keyword(s):  
Body Weight ◽  
Incidental Finding ◽  
Sodium Dodecyl ◽  
Control Group ◽  
Oral Gavage ◽  
Once Daily ◽  
Dosing Regimens ◽  
Rash2 Mice ◽  
Daily Water ◽  
Cortical Architecture

Female Tg rasH2 (CB6F1/Jic-TgrasH2@Tac) mice were administered water once daily, water twice daily with 8 or 12 hours between doses, 1% sodium dodecyl sulfate in water (1% SDS) once daily, or 1% SDS twice daily with 12 hours between doses by oral gavage at volumes of 10 ml/kg/day for 28 or 29 consecutive days. A control group of mice received no treatment and no sham manipulation. There were no significant differences in body weight or food consumption between treated groups and untreated control mice. Mean weights of spleens, livers, and thymuses were lower than control values in most groups of mice subjected to gavage. Focal or multifocal loss of thymic cortical architecture was observed in 13 of 50 mice distributed among all groups (including naïve controls), however only in one instance was this finding suggestive of a precursor to neoplasia. This study demonstrated that Tg rasH2 mice can tolerate once or twice daily gavage dosing with water or vehicle containing 1% SDS. Loss of thymic cortical architecture was a common incidental finding in female Tg rasH2 mice.

Ototoxicity associated with a once daily dose amikacin regimen in febrile neutropenic patients

1992 ◽  
Vol 29 (4) ◽  
pp. 463-464 ◽  
Author(s):  
CHRISTOPHER C. KIBBLER ◽  
PAUL H. M. McWHINNEY ◽  
PAULINE WARNER ◽  
H. GRANT PRENTICE
Keyword(s):  
Once Daily ◽  
Daily Dose ◽  
Neutropenic Patients

Treatment of hyperthyroidism with a small single daily dose of methimazole

1988 ◽  
Vol 119 (1) ◽  
pp. 139-144 ◽  
Author(s):  
Yasuo Mashio ◽  
Mutsuo Beniko ◽  
Akemi Ikota ◽  
Hiroaki Mizumoto ◽  
Haruhiko Kunita
Keyword(s):  
Divided Dose ◽  
Dose Regimen ◽  
Single Daily Dose ◽  
Once Daily ◽  
Daily Dose ◽  
The Mean ◽  
Time Required ◽  
Daily Dose Regimen ◽  
Mean Time ◽  
Immunoglobulin Levels

Abstract. A prospective randomized trial with the conventional divided doses (10 mg 3 times daily, N = 29) and a small single daily dose (15 mg once daily, N = 25) of methimazole for the treatment of Graves' hyperthyroidism was performed. Within 8 weeks, almost 80% of the patients in both groups became euthyroid. The mean time required to achieve the euthyroid state was 6.0 ± 2.8 and 6.0 ± 3.8 weeks, respectively. TSH binding inhibitor immunoglobulin was found in about 90% of the patients in both groups before methimazole treatment. However, a gradual fall of its levels was observed in nearly all patients after treatment. There was no difference in the mean levels of TSH binding inhibitor immunoglobulin between the two groups during therapy. We conclude that the single daily dose regimen of 15 mg of methimazole will control Graves' hyperthyroidism in most patients, and TSH binding inhibitor immunoglobulin levels decrease in this regimen in the same way as with the conventional divided dose regimen (10 mg 3 times daily).

A comparison of the effects on intragastric acidity of bedtime or dinnertime administration of a once daily dose of famotidine

1988 ◽  
Vol 35 (2) ◽  
pp. 203-207 ◽  
Author(s):  
V. Savarino ◽  
G. S. Mela ◽  
P. Scalabrini ◽  
G. Fera ◽  
P. Zentilin ◽  
...  
Keyword(s):  
Intragastric Acidity ◽  
Once Daily ◽  
Daily Dose

Preliminary analysis of a U.S. phase II study of the safety and tolerability of proxalutamide (GT0918) in subjects with mCRPC who had progressed on either abiraterone (Abi) or enzalutamide (Enza).

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 99-99
Author(s):  
Nicholas J. Vogelzang ◽  
Richard Levin ◽  
Arash Rezazadeh ◽  
Chandler H. Park ◽  
Britt Haley Bolemon ◽  
...  
Keyword(s):  
Phase Ii ◽  
Lipid Lowering ◽  
Early Discontinuation ◽  
Once Daily ◽  
Experimental Therapies ◽  
Daily Dose ◽  
Grade 3 ◽  
Good Treatment Option ◽  
Recommended Phase Ii Dose ◽  
Clinical Trial Information

99 Background: GT0918, an androgen receptor (AR) antagonist, is a new chemical entity with reduced drug accumulation in the CNS. In a phase I dose escalation trial (NCT02826772), GT0918 was well tolerated with some durable responses in mCRPC patients (pts) who had progressed on ≥2 lines of standard and experimental therapies. This Phase 2 was designed to study the safety and efficacy of GT0918 400 mg vs. 500 mg oral daily in mCRPC pts who had progressed on either Abi or Enza with or without prior docetaxel. Methods: Pts with histologically confirmed mCRPC who had progressed on either Abi or Enza with or without prior docetaxel were eligible and randomized to 400 mg or 500 mg of GT0918 administered once daily orally. Pts continued treatment with GT0918 at their assigned dose until disease progression, intolerable toxicities or withdrawal of consent. PSA and labs were checked monthly. Imaging scans (CT/MRI and bone scan), circulating tumor cells and cf-DNA/RNA were performed every 3 months. Results: 61 pts were enrolled at 9 US sites and randomized 1:1 to 400 mg (n = 31) or 500 mg (n = 30) daily dose. All pts had progressed on either Abi (n = 34) or Enza (n = 27). Most of the reported AEs related to GT0918 were grade 1 or 2 as per CTCAE v4.03, but 22 AEs (5.3%) were reported as grade ≥ 3, such as fatigue, increase ALT/AST, rhabdomyolysis, or muscle weakness. Some AEs were due to drug-drug interaction with lipid-lowering medications leading to early discontinuation (26.2%). As of 5 October 2020, twelve pts finished 6 cycles. Among them, three finished 12 cycles and remained on the treatment. Treatment duration showed more pts in the 400 mg cohort with stable disease (SD) on imaging (9/31 finished 6 cycles) compared to the 500 mg cohort (3/30 finished 6 cycles). Further, all three pts who finished 12 cycles had progressed on Abi indicating that GT0918 might be a good treatment option for pts who had progressed on Abi. Conclusions: Proxalutamide (GT0918) administrated orally once a day is well tolerated and resulted in SD in pts who had progressed on either Abi or Enza. The 400 mg/day will be considered as the recommended phase II dose for further clinical trials. GT0918 is warranted for pts failed either Abi or Enza. Clinical trial information: NCT03899467.

Supervising Lithium a Comparison of a Lithium Clinic, Psychiatric Out-patient Clinics, and General Practice

1988 ◽  
Vol 152 (4) ◽  
pp. 535-538 ◽  
Author(s):  
George Masterton ◽  
Mary Warner ◽  
Brian Roxburgh
Keyword(s):  
General Practice ◽  
Glomerular Filtration ◽  
Lithium Treatment ◽  
Lithium Level ◽  
Once Daily ◽  
Serum Lithium Level ◽  
Daily Dose

Supervision of lithium treatment among three groups of patients treated in different settings – at a lithium clinic, as hospital out-patients, and by a GP – was studied. The lithium clinic maintained lower levels and checked these more frequently. Elevated lithium levels were most frequent in the GP-supervised group, which also included the 13 patients with the most impaired glomerular filtration. In hospital settings GFR-impaired patients received a lower daily dose of lithium; in general practice, affected patients had a higher mean serum lithium level and were more frequently prescribed lithium once daily. We conclude that patients with glomerular impairment who require lithium should be supervised by a specialist, or at least prescribed lithium in divided daily doses.

scholarly journals Adaptive resistance of Pseudomonas aeruginosa induced by aminoglycosides and killing kinetics in a rabbit endocarditis model.

1997 ◽  
Vol 41 (4) ◽  
pp. 823-826 ◽  
Author(s):  
Y Q Xiong ◽  
J Caillon ◽  
M F Kergueris ◽  
H Drugeon ◽  
D Baron ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Single Dose ◽  
Ex Vivo ◽  
Day Treatment ◽  
Total Daily Dose ◽  
Once Daily ◽  
Adaptive Resistance ◽  
Dosing Regimens

Adaptive resistance following the first exposure to aminoglycosides is a recently described in vitro phenomenon in Pseudomonas aeruginosa and other aerobic gram-negative bacilli. We investigated the in vivo relevance of adaptive resistance in P. aeruginosa following a single dose of amikacin in the experimental rabbit endocarditis model. Rabbits with P. aeruginosa endocarditis received either no therapy (control) or a single intravenous (i.v.) dose of amikacin (80 mg/kg of body weight) at 24 h postinfection, after which they were sacrificed at 5, 8, 12, 16, or 24 h postdose. Excised aortic vegetations were subsequently exposed ex vivo to amikacin at 2.5, 5, 10 or 20 times the MIC for 90 min. In vivo adaptive resistance was identified when amikacin-induced pseudomonal killing within excised aortic vegetations was less in animals receiving single-dose amikacin in vivo than in vegetations from control animals not receiving amikacin in vivo. Maximal adaptive resistance occurred between 8 and 16 h after the in vivo amikacin dose, with complete refractoriness to ex vivo killing by amikacin seen at 12 h postdose. By 24 h postdose, bacteria within excised vegetations had partially recovered their initial amikacin susceptibility. In a parallel treatment study, we demonstrated that amikacin given once daily (but not twice daily) at a total dose of 80 mg/kg i.v. for 1-day treatment significantly reduced pseudomonal densities within aortic vegetations versus those in untreated controls. When therapy was continued for 3 days with the same total daily dose (80 mg/kg/day), amikacin given once or twice daily significantly reduced intravegetation pseudomonal densities versus those in controls. However, amikacin given once daily was still more effective than the twice-daily regimen. These data confirm the induction of aminoglycoside adaptive resistance in vivo and further support the advantages of once-daily aminoglycoside dosing regimens in the treatment of serious pseudomonal infections.

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