Loracarbef: Sinus Tissue Penetration after Single dose Administration

The underlying basis of the antibiotic treatment of sinusitis is still unclear. Critical to the use of antibiotics in patients with sinusitis is the tissue penetration of the curative agent. However, there is scant information available regarding maxillary mucosal tissue levels in patients with this disease. We present the results of plasma and sinus tissue concentrations of loracarbef in six patients and one control. Levels were taken at 2 and 3 hours after the oral administration of the medication. The mean sinus tissue level was 2.5 mcg/gm and 2.7 mcg/gm at 2 and 3 hours after administration respectively. Although therapeutic efficacy cannot be predicted by the concentrations attained in a specific body fluid or tissue, we believe that these levels are excellent based on mean inhibitory concentrations. Additional studies are underway to document the penetration of this and comparable other drugs in multiple sinuses.

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Pharmacokinetics and Buccal Mucosal Concentrations of a 15 Milligram per Kilogram of Body Weight Total Dose of Liposomal Amphotericin B Administered as a Single Dose (15 mg/kg), Weekly Dose (7.5 mg/kg), or Daily Dose (1 mg/kg) in Peripheral Stem Cell Transplant Patients

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01448-08 ◽

2009 ◽

Vol 53 (9) ◽

pp. 3664-3674 ◽

Cited By ~ 22

Author(s):

Paul O. Gubbins ◽

Jarrett R. Amsden ◽

Scott A. McConnell ◽

Elias J. Anaissie

Keyword(s):

Body Weight ◽

Stem Cell ◽

Single Dose ◽

Amphotericin B ◽

Liposomal Amphotericin ◽

Stem Cell Transplant ◽

Plasma Concentrations ◽

Cell Transplant ◽

Mucosal Tissue ◽

Tissue Concentrations

ABSTRACT The pharmacokinetics and safety of extended-interval dosing of prophylactic liposomal amphotericin B (L-AMB) in peripheral stem cell transplant recipients were evaluated. The patients received L-AMB daily at 1 mg/kg of body weight or weekly at 7.5 mg/kg or received L-AMB as a single dose (15 mg/kg). The buccal mucosal tissue concentrations of L-AMB were measured. Of the 24 patients enrolled, 5 withdrew after the initial dose due to an infusion-related reaction (n = 2) or significant increases in the serum creatinine (Scr) levels (n = 3). Weekly L-AMB dosing (7.5 mg/kg) produced mean plasma concentrations of >0.300 μg/ml for the first 7 days and >0.220 μg/ml for 7 days after the second dose. A single L-AMB dose (15 mg/kg) produced mean plasma concentrations of >0.491 μg/ml for at least 7 seven days. These concentrations are within the range of the MICs reported in the literature for susceptible strains of Candida and are at the lower limits of the MICs for Aspergillus spp. Extended-interval dosing produced buccal mucosal tissue concentrations well in excess of the MICs reported in the literature for susceptible strains of Candida and Aspergillus spp. Infusion-related reactions occurred in 24% of the patients. Baseline and end-of-study Scr, electrolyte (K+, Mg2+, PO4), and serum transaminase levels were similar across the dosage groups. Five (31%) patients met the nephrotoxicity definition prior to completion of the study. Patients in the weekly or single-dose groups experienced nephrotoxicity significantly faster than the patients in the daily dosing cohort. A weekly L-AMB dose (7.5 mg/kg) or a single L-AMB dose (15 mg/kg) produced sufficient concentrations in plasma and highly vascular tissue to warrant further studies of the safety, efficacy, and practicality of the weekly prophylactic administration of L-AMB.

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Tissue Penetration and Pharmacokinetics of Tigecycline in Diabetic Patients with Chronic Wound Infections Described by Using In Vivo Microdialysis

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01051-10 ◽

2010 ◽

Vol 54 (12) ◽

pp. 5209-5213 ◽

Cited By ~ 32

Author(s):

Catharine C. Bulik ◽

Dora E. Wiskirchen ◽

Ashley Shepard ◽

Christina A. Sutherland ◽

Joseph L. Kuti ◽

...

Keyword(s):

Steady State ◽

Protein Binding ◽

Subcutaneous Tissue ◽

Diabetic Patients ◽

Tissue Penetration ◽

Tissue Concentrations ◽

Time Curve ◽

The Mean

ABSTRACT Tissue penetration of systemic antibiotics is an important consideration for positive outcomes in diabetic patients. Herein we describe the exposure profile and penetration of tigecycline in the interstitial fluid of wound margins versus that of uninfected thigh tissue in 8 adult diabetic patients intravenously (IV) administered 100 mg and then 50 mg of tigecycline twice daily for 3 to 5 doses. Prior to administration of the first dose, 2 microdialysis catheters were inserted into the subcutaneous tissue, the first within 10 cm of the wound margin and the second in the thigh of the same extremity. Samples for determination of plasma and tissue concentrations were simultaneously collected over 12 h under steady-state conditions. Tissue concentrations were corrected for percent in vivo recovery by the retrodialysis technique. Plasma samples were also collected for determination of protein binding at 1, 6, and 12 h postdose for each patient. Protein binding data were corrected using a fitted polynomial equation. The mean patient weight was 95.1 kg (range, 63.6 to 149.2 kg), the mean patient age was 63.5 ± 9.4 years, and 75% of the patients were males. The mean values for the plasma, thigh, and wound free area under the concentration-time curve from 0 to 24 h (fAUC0-24) were 2.65 ± 0.33, 2.52 ± 1.15, and 2.60 ± 1.02 μg·h/ml, respectively. Protein binding was nonlinear, with the percentage of free drug increasing with decreasing serum concentrations. Exposure values for thigh tissue and wound tissue were similar (P = 0.986). Mean steady-state tissue concentrations for the thigh and wound were similar at 0.12 ± 0.02 μg/ml, and clearance from the tissues appeared similar to that from plasma. Tissue penetration ratios (tissue fAUC/plasma fAUC) were 99% in the thigh and 100% in the wound (P = 0.964). Tigecycline penetrated equally well into wound and uninfected tissue of the same extremity.

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Absorption of Penicillin V from Mixture Formulations. Comparison of Potassium and Benzathine Salts

Journal of International Medical Research ◽

10.1177/030006058100900307 ◽

1981 ◽

Vol 9 (3) ◽

pp. 189-190 ◽

Cited By ~ 4

Author(s):

Markku Heikinheimo ◽

Tapani Hovi

Keyword(s):

Single Dose ◽

Serum Level ◽

Potassium Salt ◽

Absorption Rate ◽

Peak Level ◽

Serum Levels ◽

Dose Administration ◽

Level Curves ◽

The Mean ◽

Adult Volunteers

The absorption rate and serum level curves of two commercial phenoxymethylpenicillin mixture preparations were compared in adult volunteers. Both the potassium salt (Primcilliri®) and the benzathine salt (V-Pen ped forte®) of V-penicillin were rapidly absorbed and the mean peak serum levels were obtained with both preparations within the first hour after single dose administration. The mean peak level obtained with the potassium salt was several-fold higher (p < 0.001) and was also reached within a shorter time than that of the benzathine preparation. These results confirm the earlier evidence, obtained with other formulae, for the superior bioavailability of the potassium salt of V-penicillin as compared to most other derivatives used in V-penicillin mixtures.

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Is the pretransplant C2 an optimum predictor of posttransplant dose for tacrolimus in renal transplantation patients?

International Journal of Pharmacokinetics ◽

10.4155/ipk-2019-0002 ◽

2019 ◽

Vol 4 (1) ◽

pp. IPK03

Author(s):

Smita Pattanaik ◽

Ashish Sharma ◽

Praveen Kumar-M ◽

Sarbpreet Singh ◽

Vikram Shetty ◽

...

Keyword(s):

Single Dose ◽

Renal Transplantation ◽

Trough Concentration ◽

Tacrolimus Concentration ◽

Spearman Correlation ◽

Dose Requirement ◽

Post Transplantation ◽

Dose Administration ◽

Post Transplant ◽

The Mean

Aim: The study evaluated whether a single dose pretransplant 2-h tacrolimus concentration (C2) could predict the post-transplantation trough concentration (C0). Materials & methods: C2 concentration of tacrolimus was measured after single-dose administration (0.1 mg/kg) in 20 patients, 4–7 days prior to renal transplantation. Tacrolimus C0 monitoring was done on post-transplant day 2, 5, 10, 15 and 30. Results: The mean C2 was 21.79 ± 16.83 ng/ml (4.25–69.46) and the mean C0 obtained 48 h after transplant was 10.2 ± 6.27 (1.63–22.07) ng/ml. The Spearman correlation between C2 and C0 was 0.71 (p < 0.01). Conclusion: Pretransplant C2 could explain only 50% of the total variation in the post-transplant dose requirement hence it may not be sole predictor of the post-transplant dose.

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Sleep improving effects of a single dose administration of a valerian/hops fluid extract. A double blind, randomized, placebo-controlled sleep-EEG study in a parallel design using the electrohypnogram

Zeitschrift für Phytotherapie ◽

10.1055/s-2008-1047853 ◽

2008 ◽

Vol 29 (S 1) ◽

Cited By ~ 4

Author(s):

W Dimpfel ◽

AA Suter

Keyword(s):

Single Dose ◽

Sleep Eeg ◽

Double Blind ◽

Dose Administration ◽

Single Dose Administration ◽

Parallel Design

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Bio-Distribution and Pharmacokinetics of Topically Administered γ-Cyclodextrin Based Eye Drops in Rabbits

Pharmaceuticals ◽

10.3390/ph14050480 ◽

2021 ◽

Vol 14 (5) ◽

pp. 480

Author(s):

Martin Kallab ◽

Kornelia Schuetzenberger ◽

Nikolaus Hommer ◽

Bhavapriya Jasmin Schäfer ◽

Doreen Schmidl ◽

...

Keyword(s):

Single Dose ◽

Drug Concentration ◽

Vitreous Humor ◽

Controlled Study ◽

Eye Drops ◽

Corneal Tissue ◽

Single Administration ◽

Local Tolerability ◽

Dose Administration ◽

Retinal Tissue

The purpose of this study was to evaluate the ocular pharmacokinetics, bio-distribution and local tolerability of γ-cyclodextrin (γCD) based irbesartan 1.5% eye drops and candesartan 0.15% eye drops after single and multiple topical administration in rabbit eyes. In this randomized, controlled study, a total number of 59 New Zealand White albino rabbits were consecutively assigned to two study groups. Group 1 (n = 31) received irbesartan 1.5% and group 2 (n = 28) candesartan 0.15% eye drops. In both groups, single dose and multiple administration pharmacokinetic studies were performed. Rabbits were euthanized at five predefined time points after single-dose administration, whereas multiple-dose animals were dosed for 5 days twice-daily and then euthanized 1 h after the last dose administration. Drug concentration was measured by using liquid chromatography-tandem mass spectrometry (LC-MS/MS) in the retinal tissue, vitreous humor, aqueous humor, corneal tissue and in venous blood samples. Pharmacokinetic parameters including maximal drug concentration (Cmax), time of maximal drug concentration (Tmax), half-life and AUC were calculated. To assess local tolerability, six additional rabbits received 1.5% irbesartan eye drops twice daily in one eye for 28 days. Tolerability was assessed using a modified Draize test and corneal sensibility by Cochet Bonnet esthesiometry. Both γCD based eye drops were rapidly absorbed and distributed in the anterior and posterior ocular tissues. Within 0.5 h after single administration, the Cmax of irbesartan and candesartan in retinal tissue was 251 ± 142 ng/g and 63 ± 39 ng/g, respectively. In the vitreous humor, a Cmax of 14 ± 16 ng/g for irbesartan was reached 0.5 h after instillation while Cmax was below 2 ng/g for candesartan. For multiple dosing, the observed Cmean in retinal tissue was 338 ± 124 ng/g for irbesartan and 36 ± 10 ng/g for candesartan, whereas mean vitreous humor concentrations were 13 ± 5 ng/g and <2 ng/g, respectively. The highest plasma concentrations of both irbesartan (Cmax 5.64 ± 4.08 ng/mL) and candesartan (Cmax 4.32 ± 1.04 ng/mL) were reached 0.5 h (Tmax) after single administration. Local tolerability was favorable with no remarkable differences between the treated and the control eyes. These results indicate that irbesartan and candesartan in γCD based nanoparticle eye drops can be delivered to the retinal tissue of the rabbit’s eye in pharmacologically relevant concentrations. Moreover, safety and tolerability profiles appear to be favorable in the rabbit animal model.

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