scholarly journals Pharmacokinetics of Caffeine following a Single Administration of Coffee Enema versus Oral Coffee Consumption in Healthy Male Subjects

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Supanimit Teekachunhatean ◽  
Nisanuch Tosri ◽  
Noppamas Rojanasthien ◽  
Somdet Srichairatanakool ◽  
Chaichan Sangdee
Keyword(s):  
Healthy Subjects ◽  
Coffee Consumption ◽  
Relative Bioavailability ◽  
Single Administration ◽  
Healthy Male ◽  
Open Label ◽  
Two Phase ◽  
The Mean ◽  
To Receive ◽  
Male Subjects

The objective of this study was to determine the pharmacokinetics of caffeine after single administration of a coffee enema versus coffee consumed orally in healthy male subjects. The study design was an open-label, randomized two-phase crossover study. Eleven healthy subjects were randomly assigned either to receive 500 mL of coffee enema for 10 minutes or to consume 180 mL of ready-to-drink coffee beverage. After a washout period of at least 10 days, all the subjects were switched to receive the alternate coffee procedure. Blood samples were collected immediately before and at specific time points until 12 hours after coffee administration in each phase. The mean caffeine content in both the coffee solution prepared for the coffee enema and the ready-to-drink coffee beverage was not statistically different. The Cmax and AUC of caffeine obtained from the coffee enema were about 3.5 times significantly less than those of the coffee consumed orally, despite having slightly but statistically faster Tmax. The t1/2 of caffeine obtained following both coffee procedures did not statistically differ. In summary, the relative bioavailability of caffeine obtained from the coffee enema was about 3.5 times significantly less than those of the coffee consumed orally.

scholarly journals Co-Administration of Vonoprazan, Not Tegoprazan, Affects the Pharmacokinetics of Atorvastatin in Healthy Male Subjects

2021 ◽  
Vol 12 ◽  
Author(s):  
Sejung Hwang ◽  
Jae-Wook Ko ◽  
Heechan Lee ◽  
Seokuee Kim ◽  
Bongtae Kim ◽  
...  
Keyword(s):  
Healthy Subjects ◽  
Clinical Laboratory ◽  
Systemic Exposure ◽  
Cytochrome P450 3A4 ◽  
Healthy Male ◽  
Open Label ◽  
Once Daily ◽  
New Class ◽  
Inhibitory Activities ◽  
Male Subjects

Potassium-competitive acid blocker is a new class of drugs inhibiting gastric acid. It is controversial that vonoprazan showed the inhibitory activities of cytochrome P450 3A4. This study aimed to evaluate the pharmacokinetics (PK) of atorvastatin and safety when atorvastatin was administered alone and co-administered with vonoprazan or tegoprazan. An open-label, multiple-dose, 3-intervention, 4-sequence, 4-period, partial replicate crossover study was conducted, and three interventions were; one is orally administered atorvastatin 40 mg alone once daily for 7 days, another is atorvastatin co-administered with vonoprazan 20 mg, and the other is atorvastatin co-administered with tegoprazan 50 mg. PK blood samples were collected up to 24 h after the last dose, and PK parameters for atorvastatin, 2-hydroxyatorvastatin and atorvastatin lactone were estimated by a non-compartmental method. Safety was evaluated, including adverse events and clinical laboratory tests. A total of 28 subjects completed the study. When atorvastatin was co-administered with vonoprazan, the systemic exposures of atorvastatin and atorvastatin lactone significantly increased, and the metabolic ratio of 2-hydroxyatorvastatin significantly decreased. Hypergastrinemia only occurred when atorvastatin was co-administered with vonoprazan. However, the plasma concentration profiles of atorvastatin, 2-hydroxyatorvastatin and atorvastatin lactone were similar when atorvastatin was administered alone or co-administered with tegoprazan. In conclusion, after multiple doses of atorvastatin co-administered with vonoprazan in healthy subjects, the systemic exposure of atorvastatin and the incidence of hypergastrinemia increased. With tegoprazan, however, those interactions were not observed.

Effect of Valine on 5-HT-mediated Prolactin Release in Healthy Volunteers, and on Mood in Remitted Depressed Patients

1995 ◽  
Vol 167 (2) ◽  
pp. 238-242 ◽  
Author(s):  
D. J. Williamson ◽  
S. F. B. McTavish ◽  
S. B. G. Park ◽  
P. J. Cowen
Keyword(s):  
Depressive Symptoms ◽  
Healthy Subjects ◽  
Antidepressant Drug ◽  
Experimental Studies ◽  
Healthy Male ◽  
Prolactin Release ◽  
Depressed Patients ◽  
Symptomatic Relapse ◽  
Male Subjects ◽  
Antidepressant Drug Treatment

BackgroundAnimal experimental studies suggest that the amino acid valine may decrease brain serotonin (5-HT) function by inhibiting the transport of the 5-HT precursor, L-tryptophan, across the blood barrier. The aim of the present study was to assess whether valine could decrease brain 5-HT function in healthy subjects and provoke symptomatic relapse in recently remitted depressed patients taking antidepressant drug treatment.MethodWe studied the effect of valine (30 g) on the prolactin (PRL) response to the 5-HT releasing agent, d-fenfluramine, in healthy male subjects and on the mood of 12 remitted depressed patients taking either selective serotonin re-uptake inhibitors (n = 10) or lithium and amitriptyline (n = 2).ResultsValine significantly lowered the PRL response to d-fenfluramine in healthy subjects. In the remitted depressives, valine caused a mild but detectable lowering of mood on a number of measures but only one patient experienced a significant relapse in mood.ConclusionsValine administration may decrease brain 5-HT neurotransmission in humans. This effect could explain the mild increase in depressive symptoms in patients taking 5-HT-potentiating drugs.

scholarly journals Pharmacokinetics (PK) and Safety of Intravenous (IV) Brincidofovir (BCV) in Healthy Adult Subjects

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S311-S311 ◽  
Author(s):  
Mary Beth Wire ◽  
Marion Morrison ◽  
Maggie Anderson ◽  
Thangam Arumugham ◽  
John Dunn ◽  
...  
Keyword(s):  
Healthy Subjects ◽  
Geometric Mean ◽  
Compartmental Analysis ◽  
Repeat Dose ◽  
Double Blind Study ◽  
Double Blind ◽  
Dose Administration ◽  
To Receive ◽  
Male Subjects ◽  
Support Evaluation

Abstract Background BCV is a lipid conjugate nucleotide that has shown rapid viral clearance in patients with adenovirus infection and improved survival in animal models of smallpox. In preclinical studies in rats, IV BCV dosed twice weekly for up to 29 days was not associated with gastrointestinal (GI), hematopoietic, hepatic, or renal toxicity. This study evaluated the safety and PK of IV BCV in healthy subjects. Methods In this double-blind study, subjects were randomized 3:1 to receive IV BCV or placebo in sequential single ascending dose cohorts (Table 1). Plasma PK samples were collected over 7 days and assayed by HPLC-MS. Plasma BCV PK parameters were determined by non-compartmental analysis and dose proportionality was assessed. Safety assessments were collected over 14 days. Results Forty healthy male subjects (18–46 years, 83% White) were enrolled and completed the study. Plasma BCV Cmax and AUC∞ increased in proportion to dose (Table 1). AEs and alanine aminotransferase (ALT) elevations were dose- and infusion duration-related (Table 1). GI AEs were mild. All AEs and ALT elevations were transient and no serious AEs occurred. Conclusion Single doses of BCV 10–50 mg administered as a 2h IV infusion were well tolerated and not associated with significant clinical or laboratory abnormalities. BCV IV 10 mg and BCV IV 50 mg achieved geometric mean plasma BCV AUC∞ similar to and 4.5-fold, respectively, values achieved with BCV oral 100 mg tablets (Cmax = 251 ng/mL and AUC∞ = 1394 ng hours/mL). These data support evaluation of repeat dose administration in healthy subjects and virally-infected patients. Disclosures M. B. Wire, Chimerix: Employee and Shareholder, Salary. M. Morrison, Chimerix: Employee and Shareholder, Salary.M. Anderson, Chimerix: Employee and Shareholder, Salary. T. Arumugham, Chimerix: Employee and Shareholder, Salary. J. Dunn, Chimerix: Employee and Shareholder, Salary. O. Naderer, Chimerix: Employee and Shareholder, Salary.

Initiating epoetin alfa (EPO) 120,000 U every three weeks (Q3W) in pts with chemotherapy (CT)-induced anemia (CIA)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 19564-19564 ◽  
Author(s):  
J. Glaspy ◽  
V. Charu ◽  
V. Moyo ◽  
M. Kamin ◽  
F. E. Wilhelm
Keyword(s):  
Randomized Study ◽  
Intervention Group ◽  
Target Range ◽  
Future Research ◽  
Final Visit ◽  
Open Label ◽  
The Mean ◽  
Dosing Intervals ◽  
To Receive ◽  
Prescribing Information

19564 Background: Emerging data suggest that initiating EPO therapy earlier (at a higher hemoglobin [Hb] trigger) in the setting of active CT may provide better maintenance of Hb within a target range with no adverse safety consequence. Reported here are the final results of the first study to explore the efficacy and safety of early vs standard intervention with EPO initiated Q3W at 120,000 U. Methods: This 16-wk open-label randomized study enrolled pts with non-myeloid malignancy, baseline (BL) Hb =11.0 and =12.0 g/dL, and CT planned for =9 wks. Pts were randomized (1:1) to receive EPO 120,000 U subcutaneously Q3W immediately (early intervention group, EIG) or when their Hb fell to <11.0 g/dL (standard intervention group, SIG). If, at any dosing visit after the first EPO dose, Hb decreased to <10.0 g/dL, pts were switched to EPO 40,000 U weekly (QW). Dose was withheld for Hb >13.0 g/dL at any dosing visit; dose was reduced for Hb >12.0 g/dL or Hb increase >1.5 g/dL in a 3-wk period (current prescribing information recommends target Hb not to exceed 12 g/dL). Hb response was defined as Percent Values in Range (PVR; the mean proportion of weekly Hb levels that were =11.0 and =13.0 g/dL) and by mean Hb change from BL. Hb data following switch to 40,000 U QW were censored. Results: A total of 136 pts were randomized (68 per group). Demographics were similar; BL Hb was 11.5 g/dL in both groups. PVR was 60% in the EIG and SIG. Mean Hb change from BL to final value on Q3W dosing was -0.1 g/dL in both groups. Among the 51 pts whose Hb fell below 11 g/dL in the SIG, their Hb decreased to a mean of 10.4 g/dL before initiation of EPO. Their subsequent mean Hb increase was 0.7 g/dL at the final visit on Q3W therapy. PRBC transfusion rates after the first 4 wks of EPO treatment were 8.8% (6/68) and 7.8% (4/51) for the EIG and SIG, respectively. In the EIG vs SIG, EPO was withheld in 38% vs 22% of pts and reduced in 43% vs 26% of pts. Two deaths and 6 clinically relevant TVEs while on EPO treatment were reported in each group. Conclusions: This is the first study to show EPO may be initiated at 120,000 U every 3 wks. Hb outcomes in the EIG and SIG were similar. These data provide further evidence that half-life of erythropoietins may not correlate with their effectiveness when used at extended dosing intervals. Future research is warranted. No significant financial relationships to disclose.

scholarly journals Induction of theophylline clearance by rifampin and rifabutin in healthy male volunteers.

1996 ◽  
Vol 40 (8) ◽  
pp. 1866-1869 ◽  
Author(s):  
J G Gillum ◽  
J M Sesler ◽  
V L Bruzzese ◽  
D S Israel ◽  
R E Polk
Keyword(s):  
Treatment Phase ◽  
Pharmacokinetic Parameters ◽  
Theophylline Clearance ◽  
Healthy Male ◽  
Time Curve ◽  
Concentration Time ◽  
Male Volunteers ◽  
Hepatic Microsomal Enzyme ◽  
The Mean ◽  
To Receive

Rifampin and rifabutin induce the metabolism of many drugs, which may result in subtherapeutic concentrations and failure of therapy. However, differences between rifabutin and rifampin in potency of induction, and the specific enzymes which are altered, are not clear. This study, involving 12 adult male volunteers, compared the effects of 14-day courses of rifampin and rifabutin on clearance of theophylline, a substrate for the hepatic microsomal enzyme CYP1A2. Subjects were given oral theophylline solution (5 mg/kg of body weight) on day 1 and then randomized to receive daily rifampin (300 mg) or rifabutin (300 mg) on days 3 to 16. Theophylline was readministered as described above on day 15. The first treatment sequence was followed by a 2-week washout period; subjects then received the alternative treatment. Theophylline concentrations were determined for 46 h after each dose, and pharmacokinetic parameters were determined. One subject developed flu-like symptoms while taking rifabutin and withdrew voluntarily. Results from the remaining 11 subjects are reported. Compared with the baseline, the mean area under the concentration-time curve (AUC) (+/- standard deviation) for theophylline declined significantly following rifampin treatment (from 140 +/- 37 to 100 +/- 24 micrograms . h/ml, P <0.001); there was no significant change following rifabutin treatment (136 +/- 48 to 128 +/- 45 micrograms.h/ml). Baseline theophylline AUCs before each treatment phase were not different. A comparison of equal doses of rifampin and rifabutin administered to healthy volunteers for 2 weeks indicates that induction of CYP1A2, as measured by theophylline clearance, is significantly less following rifabutin treatment than it is following rifampin treatment. However, the relative induction potency for other metabolic enzymes remains to be investigated.

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