Bioavailability of Temazepam: Comparison of Four 7.5-mg Capsules with a Single 30-mg Capsule

OBJECTIVE: To compare the bioavailability of four temazepam 7.5-mg capsules (Restoril, Sandoz Pharmaceuticals) with that of a single temazepam 30-mg capsule. DESIGN: Single-dose, open-label, two-period, crossover (replicated Latin square). SETTING: Domiciled environment for clinical testing. PARTICIPANTS: Twenty-six healthy male volunteers aged 18–40 years; 25 completed the study. INTERVENTIONS: Subjects randomly received either four temazepam 7.5-mg capsules or one temazepam 30-mg capsule. Blood samples were drawn at various time points after each period (0-48 h), and analyzed for plasma concentration of temazepam. The washout period between doses was five days. MAIN OUTCOME MEASUREMENTS: Five parameters of both dosage forms were compared: (1) area under curve (AUC), (2) peak concentration (Cmax), (3) time to peak concentration (Tmax), (4) apparent rate constant for absorption, and (5) lag time for appearance of drug in plasma. Statistical procedures included ANOVA, power analysis, and confidence limits. RESULTS: The mean AUC for the four 7.5-mg capsules and one 30-mg capsule differed by less than 2 percent and the mean Cmax differed by less than 14 percent for the two dosage strengths; neither of these differences reached statistical significance (p>0.05). The 7.5-mg capsules reached peak plasma concentrations significantly faster than the 30-mg dosage form (mean Tmax 1.18 and 1.73 h, respectively; p=0.01). CONCLUSIONS: The two formulations of temazepam were bioequivalent with respect to the extent of bioavailability. Regarding the rate of absorption, however, the 7.5-mg capsules reached peak plasma concentrations significantly faster than the 30-mg dosage form.

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Oral Bioavailability of Candesartan Cilexetil Suspension

Journal of Pharmacy Technology ◽

10.1177/875512250702300503 ◽

2007 ◽

Vol 23 (5) ◽

pp. 270-274 ◽

Cited By ~ 1

Author(s):

Renli Teng ◽

Anna-Carin Hansson ◽

Inger Börjesson

Keyword(s):

Candesartan Cilexetil ◽

Peak Plasma ◽

Plasma Concentrations ◽

Relative Bioavailability ◽

Maximum Plasma ◽

Open Label ◽

Serious Adverse Events ◽

Time To Peak ◽

Period 2 ◽

Elimination Half

Background: Candesartan cilexetil is a prodrug that is converted to candesartan during absorption from the gastrointestinal tract. Candesartan is a potent, orally active, specific angiotensin II type 1 receptor antagonist that has become a well-accepted treatment for hypertension. Pediatric patients often require alternative dosage forms, as candesartan cilexetil is not yet commercially available as a liquid formulation. Objective: To determine the relative bioavailability of candesartan by comparing a candesartan cilexetil tablet (reference formulation) with an oral candesartan cilexetil suspension (test formulation). Methods: In an open-label, randomized, 2 period, 2 treatment crossover study, 24 healthy volunteers were given a 32 mg candesartan cilexetil tablet and a 32 mg candesartan cilexetil suspension with a 7 day washout period between treatments. Results: Pharmacokinetic analyses showed that the mean relative bioavailability of the candesartan cilexetil commercial 32 mg tablet compared with the suspension of 32 mg candesartan cilexetil was 93%. The 90% CIs of the plasma AUC for the tablet versus suspension (0.861 and 0.998, respectively) were well within the bioequivalence criteria of 80–125%. Administration of candesartan cilexetil suspension was associated with a 17% increase in the maximum plasma concentration (Cmax) relative to the tablet administration (643 vs 523 nM/L, respectively). The 90% CIs on the ratio of mean Cmax for the tablet and suspension were 0.738 and 0.914, respectively. Mean time to peak plasma concentrations (tmax) after suspension administration was 3.1 hours, whereas the tablet resulted in a mean tmax of 3.9 hours. No significant differences in elimination half-life were observed between the 2 formulations. Both formulations were well tolerated, and no serious adverse events were reported. Conclusions: These results demonstrate that administration of candesartan cilexetil suspension achieves an extent of absorption and tolerability that is comparable with those of orally administered candesartan cilexetil tablets.

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Rectal Administration of Ibuprofen: Comparison of Enema and Suppository Form

Drug Research ◽

10.1055/a-1577-2955 ◽

2021 ◽

Author(s):

Budi Prasaja ◽

Yahdiana Harahap ◽

Monika Sandra ◽

Irene Iskandar ◽

Windy Lusthom ◽

...

Keyword(s):

Phase 1 ◽

Rectal Administration ◽

Pharmacokinetic Parameters ◽

P Value ◽

Open Label ◽

Post Dose ◽

Anova Model ◽

Equal Dose ◽

Rate Of Absorption ◽

The Mean

AbstractIbuprofen is a widely used and well-tolerated analgesic and antipyretic. It is desirable to have a formulation with a rapid rate of absorption because it is required for rapid pain relief and temperature reduction. Previous studies have described the pharmacokinetic profiles of ibuprofen suppository and the mean peak times of ibuprofen suppository were around 1.8 hours, indicating a slower rate of absorption. The aim of this study is to compare the pharmacokinetic parameters of rectal administration of ibuprofen between enema and suppository form in order to provide evidence for the faster absorption rates of ibuprofen enema. This study was a phase-1 clinical study, open-label, randomized and two-way crossover with one-week washout period comparing the absorption profile of equal dose of ibuprofen administered rectally in two treatment phases: ibuprofen suppository and enema. Blood samples were collected post dose for pharmacokinetic analyses. Tmax was analyzed using a Wilcoxon matched paired test. A standard ANOVA model, appropriate for bioequivalence studies was used and ratios of 90% confidence intervals were calculated. This study showed that Tmax for ibuprofen enema was less than half that of ibuprofen suppository (median 40 min vs. 90 min, respectively; p-value=0.0003). Cmax and AUC0–12 for ibuprofen enema were bioequivalent to ibuprofen suppository, as the ratio of test/reference=104.52%, 90% CI 93.41–116.95% and the ratio of test/reference=98.12%, 90%CI 93.34–103.16%, respectively, which fell within 80–125% bioequivalence limit. The overall extent of absorption was similar to the both, which were all well tolerated. In terms of Tmax, Ibuprofen enema was absorbed twice as quickly as from ibuprofen suppository. Therefore it is expected that an ibuprofen enema may provide faster onset of analgesic and antipyretic benefit.

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Comparative changes in plasma concentrations of progesterone, oestradiol and LH during the ovulatory cycle in a multiple ovulating male line and a single ovulating traditional line of turkeys

Reproduction ◽

10.1530/rep.0.1230127 ◽

2002 ◽

pp. 127-133 ◽

Cited By ~ 4

Author(s):

S Buchanan ◽

GW Robertson ◽

PM Hocking

Keyword(s):

Peak Plasma ◽

Ovarian Tissue ◽

Plasma Concentrations ◽

High Growth ◽

Correlated Response ◽

Ovulatory Cycle ◽

Plasma Progesterone ◽

Multiple Ovulation ◽

Male Line ◽

The Mean

The aim of this study was to compare the profile of circulating concentrations of LH, progesterone and oestradiol in a multiple ovulating male line with that of a single ovulating line of traditional turkeys. Plasma samples from seven traditional and 12 male-line turkeys were obtained every 3 h for 36 h. Male-line and traditional turkeys had single peaks of LH and progesterone that were of similar duration in both lines. The mean height of the plasma peaks of LH and progesterone were similar in the two lines and there was no detectable peak plasma oestrogen concentration. Mean plasma concentrations of LH and oestrogen were higher in single compared with multiple ovulating turkeys, whereas there were no differences in mean plasma progesterone concentrations. The results indicate that the multiple ovulation state in genetically selected high-growth lines of turkey may be the result of a correlated response in the steroidogenic capacity of ovarian tissue associated with low plasma concentrations of oestrogen rather than of a disturbance in the hormone profile of the ovulatory cycle.

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Bioavailability of Paediatric Mixtures Containing Phenoxymethylpenicillin Calcium or Potassium Salt

Journal of International Medical Research ◽

10.1177/030006058201000512 ◽

1982 ◽

Vol 10 (5) ◽

pp. 379-382 ◽

Cited By ~ 2

Author(s):

Kari Soininen ◽

Hannu Allonen ◽

Juhani Posti

Keyword(s):

Potassium Salt ◽

Calcium Salt ◽

Healthy Adult ◽

Peak Plasma ◽

Peak Plasma Concentration ◽

Salt Mixture ◽

Time To Peak ◽

Aqueous Mixture ◽

The Mean ◽

Adult Volunteers

The bioavailability of the calcium and potassium salts of Phenoxymethylpenicillin (dose 38,000 I.U./kg) was investigated in eight healthy adult volunteers. Administration of the calcium salt as an aqueous oral mixture resulted in a mean peak plasma concentration of 8·52 mg/l (SD 1·96) and that of the potassium salt mixture in a concentration of 8·40 mg/ml (SD 2·61), p > 0·1. The median time-to-peak levels were 0·75 h and 1·0 h, respectively (p > 0·1). The mean AUC for the calcium salt mixture was 16·94 mg·h/l (SD 3·31) and for the potassium salt 15·84 mg·h/l (SD 4·76), p > 0·09. These findings confirm that an aqueous mixture of calcium phenoxymethylpenicillin is equivalent to a mixture of potassium Phenoxymethylpenicillin.

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Ibuprofen: Plasma Concentrations in Man

Journal of International Medical Research ◽

10.1177/030006058501300110 ◽

1985 ◽

Vol 13 (1) ◽

pp. 68-73 ◽

Cited By ~ 15

Author(s):

G M E Janssen ◽

J F Venema

Keyword(s):

Side Effects ◽

Crossover Study ◽

Plasma Levels ◽

Healthy Subjects ◽

Peak Plasma ◽

Plasma Concentrations ◽

Repeated Dose ◽

Similar Range ◽

The Mean ◽

Peak Value

The plasma levels of Ibuprofen were measured in five healthy subjects who took 600 mg tablets of Ibuprofen twice daily, three times daily and four times daily in a crossover study. Peak plasma levels were obtained 1 hour after the first dose in all but one subject (slow absorber), the mean peak value being 51·3 μg.ml−1 (range 39·4–63·7 μg.ml−1). After the repeated dose regimens of two, three or four times daily of ibuprofen, the peak levels achieved were in a similar range to those seen after the first dose: Twice daily 39·4–66·4 μg.ml−1 Three times daily 43·6–63·3 μg.ml−1 Four times daily 44·1–58·4 μg.ml−1 There was no evidence of accumulation of the drug and no side-effects occurred during the trial.

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81 Bioequivalence of a Manipulation-Resistant Immediate-Release Amphetamine Sulfate Formulation Compared with Reference Standard

CNS Spectrums ◽

10.1017/s1092852919000609 ◽

2019 ◽

Vol 24 (1) ◽

pp. 216-216

Author(s):

Steve Caras ◽

Terrilyn Sharpe

Keyword(s):

Single Dose ◽

Healthy Volunteers ◽

Peak Concentration ◽

Immediate Release ◽

Open Label ◽

Time Curve ◽

Time To Peak ◽

Amphetamine Sulfate ◽

Quantifiable Concentration ◽

Funding Acknowledgements

AbstractStudy ObjectivesWe compared the bioavailability of racemic amphetamine (d-amphetamine and l-amphetamine) from a manipulation-resistant immediate-release (IR) amphetamine sulfate capsule (AR19) versus amphetamine sulfate IR tablets (reference).MethodIn this open-label, randomized, two-period, two-treatment, two-sequence, crossover study, 36 healthy volunteers aged 18–45 received a single dose (20-mg capsule) of AR19 in one period and a single dose (2 x 10-mg tablets) of reference in another period, after a 10-hour overnight fast. Each drug administration was separated by a washout period of at least 6days. Bioequivalence for d- and l-amphetamine was assessed using time to peak concentration (Tmax), peak concentration in plasma (Cmax), and area under the plasma concentration–time curve from time-zero to the time of the last quantifiable concentration (AUClast) and extrapolated to infinity (AUCinf).ResultsAll 36 volunteers completed both treatment sequences. Mean (standard deviation; SD) Tmax for d- and l-amphetamine was similar for AR19 (2.84[1.05]; 3.05[1.22], respectively) and reference (2.52[0.75]; 2.75[1.00], respectively). The geometric least-squares mean ratios and 90% confidence intervals were within the boundary of 80%–125% for bioequivalence for Cmax (d-amphetamine, 98.35% [96.12–100.64]; l-amphetamine, 98.82% [96.42–101.28]), AUClast (d-amphetamine, 99.45% [96.92–102.05]; l-amphetamine, 99.29% [96.55–102.10]), and AUCinf (d-amphetamine, 99.50%[96.77–102.30]; l-amphetamine, 99.23% [96.06–102.50]). A total of 13 mild adverse events were reported by 7 volunteers (AEs; AR19, n=5; reference, n=8). No serious AEs were reported.ConclusionAR19 was well tolerated and was bioequivalent to reference when administered as a 20-mg dose in healthy volunteers.Funding Acknowledgements: This study was funded by Arbor Pharmaceuticals, LLC.

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Opposite Effects of Single-Dose and Multidose Administration of the Ethanol Extract of Danshen on CYP3A in Healthy Volunteers

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/730734 ◽

2013 ◽

Vol 2013 ◽

pp. 1-8 ◽

Cited By ~ 14

Author(s):

Furong Qiu ◽

Jian Jiang ◽

Yueming Ma ◽

Guangji Wang ◽

Chenglu Gao ◽

...

Keyword(s):

Single Dose ◽

Healthy Volunteers ◽

Plasma Concentrations ◽

In Vitro Study ◽

Ethanol Extract ◽

Tanshinone Iia ◽

Open Label ◽

The Mean

The aim of this study was to investigate the effect of single- and multidose administration of the ethanol extract of danshen on in vivo CYP3A activity in healthy volunteers. A sequential, open-label, and three-period pharmacokinetic interaction study design was used based on 12 healthy male individuals. The plasma concentrations of midazolam and its metabolite 1-hydroxymidazolam were measured. Treatment with single dose of the extract caused the meanCmaxof midazolam to increase by 87% compared with control. After 10 days of the danshen extract intake, the mean AUC0–12,Cmax, andt1/2of midazolam were decreased by 79.9%, 66.6%, and 43.8%, respectively. The mean clearance of midazolam was increased by 501.6% compared with control. The in vitro study showed that dihydrotanshinone I in the extract could inhibit CYP3A, while tanshinone IIA and cryptotanshinone could induce CYP3A. In conclusion, a single-dose administration of the danshen extract can inhibit intestinal CYP3A, but multidose administration can induce intestinal and hepatic CYP3A.

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Open-Label, Dose Escalation Study of the Safety and Pharmacokinetic Profile of Tefibazumab in Healthy Volunteers

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.49.3.959-962.2005 ◽

2005 ◽

Vol 49 (3) ◽

pp. 959-962 ◽

Cited By ~ 20

Author(s):

Sandra Reilley ◽

Eric Wenzel ◽

Laurie Reynolds ◽

Beth Bennett ◽

Joseph M. Patti ◽

...

Keyword(s):

Healthy Volunteers ◽

Dose Escalation ◽

Maximum Concentration ◽

Dose Range ◽

Plasma Concentrations ◽

Open Label ◽

Serious Adverse Events ◽

Dose Escalation Study ◽

Label Dose ◽

The Mean

ABSTRACT Tefibazumab (Aurexis) is a humanized monoclonal antibody being evaluated as adjunctive therapy for the treatment of Staphylococcus aureus infections. This open-label, dose escalation study evaluated the safety and pharmacokinetics of tefibazumab in 19 healthy volunteers aged 18 to 69 years. Each subject received a single administration of tefibazumab at a dose of 2, 5, 10, or 20 mg/kg of body weight infused over 15 min. Plasma samples for pharmacokinetic assessments were obtained before infusion as well as 1, 6, 12, and 24 h and 3, 4, 7, 21, 28, 42, and 56 days after dosing. Plasma concentrations of tefibazumab were detected 1 h after the end of the infusion, with a mean maximum concentration of drug in serum (C max) of 59, 127, 252, and 492 μg/ml following doses of 2, 5, 10, and 20 mg/kg, respectively. The median time to maximum concentration of drug in serum (T max) was 1.0 h for each dose. The mean elimination half-life (t 1/2) was approximately 22 days. The volume of distribution (V) was 4.7, 6.7, 7.2, and 7.2 liters after doses of 2, 5, 10, and 20 mg/kg, respectively. Clearance (CL) was 6.0, 9.2, 10.2, and 9.9 ml/hr, respectively. At the highest dose, plasma levels of tefibazumab were >100 μg/ml for 21 days. On day 56, the mean plasma concentrations were 6.3, 10.0, 16.4, and 30.5 μg/ml for the 2, 5, 10, and 20 mg/kg doses, respectively. Tefibazumab exhibited linear kinetics across doses of 5, 10, and 20 mg/kg. No anti-tefibazumab antibodies were detected after dosing in any subject. There were no serious adverse events, and tefibazumab was well tolerated over the entire dose range.

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Bioequivalence of levamlodipine besylate tablets in healthy Chinese subjects: A single-dose and two-period crossover randomized study

10.21203/rs.3.rs-47842/v2 ◽

2020 ◽

Author(s):

Li Xin ◽

Chenjing Wang ◽

Ting Li ◽

Yanping Liu ◽

Shuqin Liu ◽

...

Keyword(s):

Single Dose ◽

Randomized Study ◽

Plasma Concentrations ◽

Bioequivalence Study ◽

Pharmacokinetic Parameters ◽

Open Label ◽

Liquid Chromatography Tandem Mass ◽

The Mean ◽

Healthy Chinese ◽

Chinese Subjects

Abstract Background: Levamlodipine, a calcium channel blocker, has been show act as a cardiovascular drug. To compare the pharmacokinetic parameters between levamlodipine (test formulation) at a single dose of 5 mg and amlodipine (reference formulation) at a single dose of 10 mg, the bioequivalence study was carried out.Methods: A single-dose randomized, open-label, two-period crossover study was designed in healthy Chinese subjects. 48 subjects were divided into fasted and fed groups equally. The subjects randomly received the test or reference formulations at the rate of 1:1. Following a 21-day washout period, the alternative formulations were received. The blood samples were collected at 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 24, 36, 48, 72, 96, 120, 144, 168 hours later. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was applied to determine the plasma concentrations of levamlodipine. Adverse events were recorded.Results: The 90% confidence intervals (CIs) of the ratio of geometric means (GMRs) of Cmax, AUC0-t, and AUC0-∞ under both fasted and fed conditions were within the prespecified bioequivalence limits between 80~125%. Under fasted conditions, 24 subjects were enrolled and completed the study. The mean Cmax was (2.70±0.49) ng/mL, AUC0-t was (141.32±36.24) ng×h/mL and AUC0-∞ was (157.14±45.65) ng×h/mL after a single dose of 5 mg levamlodipine. The mean Cmax was (2.83±0.52) ng/mL, AUC0-t was (153.62±33.96) ng×h/mL and AUC0-∞ was (173.05±41.78) ng×h/mL after a single dose of 10 mg amlodipine. Under fed conditions, 24 subjects were enrolled and completed the study. The mean Cmax was (2.73±0.55) ng/mL, AUC0-t was (166.93±49.96) ng×h/mL and AUC0-∞ was (190.99±70.89) ng×h/mL after a single dose of 5 mg levamlodipine. The mean Cmax was (2.87±0.81) ng/mL AUC0-t was (165.46±43.58) ng×h/mL and AUC0-∞ was (189.51±64.70) ng×h/mL after a single dose of 10 mg amlodipine. Serious adverse event was not observed.Conclusion: The trial confirmed that levamlodipine at a single dose of 5 mg and amlodipine at a single dose of 10 mg were bioequivalent under both fasted condition and fed condition.Trial registration: Cinicaltrials, NCT04411875. Registered 3 June 2020 - Retrospectively registered, https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S0009W1Q&selectaction=Edit&uid=U00050YQ&ts=3&cx=-6iqkm8

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A Randomized, Double-Blind, Double-Dummy, Placebo-Controlled, Intranasal Human Abuse Potential Study of Oxycodone ARIR, a Novel, Immediate-Release, Abuse-Deterrent Formulation

Pain Medicine ◽

10.1093/pm/pny043 ◽

2018 ◽

Vol 20 (4) ◽

pp. 747-757 ◽

Cited By ~ 4

Author(s):

Lynn R Webster ◽

Matthew Iverson ◽

Carmela Pantaleon ◽

Michael D Smith ◽

Eric R Kinzler ◽

...

Keyword(s):

Peak Concentration ◽

Plasma Concentrations ◽

Immediate Release ◽

Abuse Potential ◽

Health Concern ◽

Prescription Opioid ◽

Double Blind ◽

Time To Peak ◽

Potential Study ◽

Drug Liking

Abstract Objective Prescription opioid abuse continues to be a public health concern. Oxycodone ARIR is an immediate-release (IR) oxycodone tablet composed of multiple overlapping barriers that deter manipulation of the tablet for non-oral abuse. Design This randomized, double-blind, double-dummy, active- and placebo-controlled, four-way crossover, intranasal human abuse potential study assessed the pharmacodynamics and pharmacokinetics of crushed intranasal oxycodone ARIR compared with crushed intranasal IR oxycodone and intact oral oxycodone ARIR. Outcome Measures Pharmacodynamic end points included mean maximum drug liking (Emax), as measured by subjects on a bipolar 100-mm visual analog scale (primary), and desire to take the drug again, overall drug liking, drug high, and good effects (secondary). Pharmacokinetic assessments included peak concentration and time to peak concentration. Results Twenty-nine subjects completed the treatment phase. Crushed intranasal oxycodone ARIR demonstrated a significant reduction of 46.9% and 23.4% in drug liking Emax compared with crushed intranasal IR oxycodone and intact oral oxycodone ARIR, respectively (P < 0.0001 for both). Significant reductions also were observed in desire to take the drug again, drug high, overall drug liking, and good effects when comparing crushed intranasal oxycodone ARIR with crushed intranasal IR oxycodone and intact oral oxycodone ARIR (P < 0.001 for all). Crushed intranasal oxycodone ARIR exhibited lower peak oxycodone plasma concentrations and slower time to peak concentration compared with crushed intranasal IR oxycodone and intact oral oxycodone ARIR. All treatments were well tolerated; adverse effects were typical of opioids or intranasal administration. Conclusions These data indicate that oxycodone ARIR has the potential to reduce abuse via the intranasal route.

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