Pharmacokinetic and local tissue disposition of [14C]sodium diclofenac following iontophoresis and systemic administration in rabbits

Hui, Xiaoying; Anigbogu, Angela; Singh, Parminder; Xiong, Glen L.; Poblete, Nicholas; Liu, Puchun; Maibach, Howard I.

doi:10.1002/jps.1079

Cited by 35 publications

(17 citation statements)

References 23 publications

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“…In contrast, most of the drug found in the SF of the treated site had been delivered by direct penetration from the dosage site, with only a small portion delivered by the systemic circulation. Similar conclusions can be found elsewhere [8,10,14] . All of these observations imply that cutaneous circulation is not always an infinite "sink," and that a drug may not be completely removed from the stratum corneum, epidermis, and dermis.…”

Section: Discussionsupporting

confidence: 92%

Pharmacokinetic studies of meloxicam following oral and transdermal administration in Beagle dogs

Yuan

Chen

et al. 2009

Acta Pharmacol Sin

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Aim:The potential for topical delivery of meloxicam was investigated by examining its pharmacokinetic profiles in plasma and synovial fluid following oral and transdermal administration in Beagle dogs. Methods: The experiment was a two-period, crossover design using 6 Beagle dogs. Meloxicam tablets were administered orally at a dose of 0.31 mg/kg, and meloxicam gel was administered transdermally at a dose of 1.25 mg/kg. Drug concentrations in plasma and synovial fluid were determined by liquid chromatography-tandem mass spectrometry (LC/MS/MS). The pharmacokinetic parameters were calculated using the Topfit 2.0 program. Results: The pharmacokinetic results showed that AUC 0-t (23.9±8.26 µg·h·mL -1 ) in plasma after oral administration was significantly higher than after transdermal delivery (1.00±0.43 µg·h·mL -1 ). In contrast, the ratio of the average concentration in synovial fluid to that in plasma following transdermal administration was higher than that for an oral delivery. The synovial fluid concentration in the treated leg was much higher than that in the untreated leg, whereas the synovial fluid concentration in the untreated leg was similar to the plasma concentration. Conclusion: The high concentration ratio of synovial fluid to plasma indicates direct penetration of meloxicam following topical administration to the target tissue. This finding is further supported by the differences observed in meloxicam concentrations in synovial fluid in the treated and untreated joints at the same time point. Our results suggest that transdermal delivery of meloxicam is a promising method for decreasing its adverse systemic effects.

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Section: Discussionsupporting

confidence: 92%

Pharmacokinetic studies of meloxicam following oral and transdermal administration in Beagle dogs

Yuan

Chen

et al. 2009

Acta Pharmacol Sin

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“…Thus, unbound concentration from subcutaneous microdialysis was multiplied by a factor, 200, to compare with our serum result. This factor is supported as our estimated total subcutaneous concentration of 18,840 ng/mL is comparable to a previous study with direct measurement of ~11,000 ng/mL subcutaneous diclofenac after iontophoresis (8).…”

Section: F I G U Re 5 Av E R a G E M I C Ro D I A L Y S A T E L E Vsupporting

confidence: 90%

“…In comparing WEDD ® active delivery with passive, the trend indicates that active delivery produces tissue concentrations more than two-fold higher, and faster, than passive delivery ( Figure 5). However, minimal levels in the subcutaneous tissue may be surprising when compared to similar studies that we have conducted with Granisetron (16) and another study with diclofenac (8). The anticipated subcutaneous concentrations of diclofenac were about 5,000-10,000 ng/mL.…”

Section: In Vivo Iontophoretic Delivery Of Diclofenac Potassiummentioning

confidence: 61%

“…It was concluded that there is a substantial benefit in using the potassium salt of diclofenac, with efficiency nearly two-fold higher than that found using a comparable concentration of the sodium salt (Table 1). Therefore, by employing the potassium salt form, the total dosage of the Hui et al study (8) was possible using much less current. In the second part of the in vitro study, the effect of excipients added to a formulation containing 20 mg/mL diclofenac potassium was investigated.…”

Section: In Vitro Iontophoretic Delivery Of Diclofenacmentioning

confidence: 99%

“…This technique offers an advantage of delivering larger quantities of a given drug when compared to passive delivery (8). In a previous study by Hui et al, transdermal iontophoresis was found to facilitate the direct penetration of diclofenac sodium to deeper tissue, as measured by radiolabeling techniques in extracted tissue samples (8).…”

Section: Introductionmentioning

confidence: 99%

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Subcutaneous concentrations following topical iontophoretic delivery of diclofenac

et al. 2012

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A self-contained Wearable Electronic Disposable Drug Delivery (WEDD ® ) patch was used to demonstrate that diclofenac levels delivered by iontophoresis are greater than estimated minimal effective concentrations in local subcutaneous tissue and are also greater than either passive transdermal or intravenous delivery using hairless rats. In vitro iontophoretic delivery was evaluated to optimize donor cell formulation using Franz diffusion cells and 1000 NMWL Millipore ultrafiltration membrane. In vivo animal studies were done using patches powered with a 4-volt system, consisting of a 1-volt Zn anode and Ag/AgCl cathode with built in 3-volt lithium battery. Blood and microdialysis samples were collected at different time points after patch application. Current levels increased to 1.0 mA at 30 min, then fell to a steady state of ~ 0.4 mA. Both WEDD ® and passive patches produced measurable levels of diclofenac in the subcutaneous tissue below the application site (C max ± SE = 113.3 ± 61.7 ng/mL and 36.3 ± 15.9 ng/mL, respectively). The dose delivered in six hours was calculated to be 0.226 ± 0.072 mg and 0.430 ± 0.048 mg in passive and iontophoretic delivery, respectively. Diclofenac was not detected in the subcutaneous tissue after intravenous administration of 1.5 mg/kg diclofenac solution. The trend indicates that WEDD ® can be used to successfully deliver diclofenac to subcutaneous tissue to concentrations higher when compared to either passive delivery or intravenous dosing of 1.5 mg/kg.

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Topical and Systemic Drug Delivery Systems for Targeted Therapy

Häfeli

Kale

2009

Peripheral Receptor Targets for Analgesia

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Pharmacokinetic and local tissue disposition of [14C]sodium diclofenac following iontophoresis and systemic administration in rabbits

Cited by 35 publications

References 23 publications

Pharmacokinetic studies of meloxicam following oral and transdermal administration in Beagle dogs

Pharmacokinetic studies of meloxicam following oral and transdermal administration in Beagle dogs

Subcutaneous concentrations following topical iontophoretic delivery of diclofenac

Topical and Systemic Drug Delivery Systems for Targeted Therapy

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