Pharmacokinetics and Safety of Continuously Applied
Pharmacokinetics and Safety of Continuously Applied
The pharmacokinetics, safety, and tolerability of four topical lidocaine patches 5% continuously applied for 72 hours and changed every 12 or 24 hours were examined.
In this randomized, prospective, multiple-dose, open-label pharmacokinetic study, lidocaine patches were applied to healthy men and women for three consecutive days. Ten subjects received four lidocaine patches every 24 hours (group 1), and 10 subjects received four patches every 12 hours (group 2). Serial samples of venous blood were obtained to determine pharmacokinetic data. Overall tolerability and safety were assessed, and skin sensory testing was conducted to determine whether local anesthetic activity was produced.
The mean maximum plasma lidocaine concentrations at steady state with lidocaine patches applied in groups 1 and 2 were 186 and 225 ng/mL, respectively, compared with the reported mean maximum plasma concentration of 130 ng/mL with the labeled dosage (12 hr/day). The area under the concentration time curve for one dosage interval at steady state was 3550 and 4506 ng·hr/mL for groups 1 and 2, respectively. No loss in sensation at the application site was reported. No patient had edema, and most cases of erythema were very slight. No systemic adverse events were judged to be related to the patches.
Continuous application for 72 hours of four lidocaine patches 5%, changed every 12 or 24 hours, produced plasma lidocaine concentrations that remained well below those that typically produce antiarrhythmic effects or toxicity. Mild application-site erythema occurred in most patients, but no systemic adverse reactions were judged to be related to the patches. No loss in sensation at the application site was reported.
The lidocaine patch 5% (Lidoderm, Endo Pharmaceuticals, Chadds Ford, PA) is a targeted peripheral analgesic designed to treat peripheral neuropathic pain with minimal risk of systemic adverse effects. The patch facilitates lidocaine diffusion across the skin, where the drug binds to sodium channels that are present in abnormally high numbers on hyperactive or damaged nociceptors. When bound to these sodium channels, lidocaine reduces the abnormal ectopic discharges produced by damaged and dysfunctional peripheral nerves and interrupts conduction of the pain signal, thus alleviating pain. This system prevents lidocaine from entering the plasma in any clinically meaningful concentrations.
The lidocaine patch 5% is labeled for the treatment of the severe neuropathic pain of postherpetic neuralgia (PHN). PHN is the most frequently encountered neurologic disorder associated with herpes zoster (shingles). A chronic neuropathic pain disorder, PHN is characterized by burning or paroxysmal pain, exquisite skin sensitivity, abnormal pain perception, sensory loss, allodynia, and hyperalgesia and can significantly compromise a patient's quality of life. Recent studies have confirmed the safety and efficacy of the lidocaine patch for the relief of PHN with the maximum labeled dosage of three patches applied to the painful, intact skin for 12 hours per day (12 hours on and 12 hours off per 24-hour period), as well as extended application of up to four patches for 18 hours per day.
Because of the refractory nature of neuropathic pain and its substantial impact on the quality of life, it is not surprising that patients with a good response to the lidocaine patch are reluctant to remove the patch after 12 hours, fearing that the pain will return. Further, the success of this treatment modality in PHN has led clinicians to explore its utility in other pain states (e.g., complex regional pain syndrome, postmastectomy pain, postthoracotomy pain, a variety of peripheral neuropathies, myofascial pain, low-back pain, and osteoarthritis). Optimal dosage for these conditions may require more than three patches to cover the most painful area and application for longer than 12 hours per day. This study, in which four lidocaine patches were applied for 24-hour periods (both once daily and every 12 hours) on three consecutive days, was designed to assess the safety, tolerability, and pharmacokinetics of continuous (24 hours per day) application of the lidocaine patch. In addition, skin sensory testing was performed under the patch to reconfirm that the lidocaine patch does not produce an anesthetic effect.
The pharmacokinetics, safety, and tolerability of four topical lidocaine patches 5% continuously applied for 72 hours and changed every 12 or 24 hours were examined.
In this randomized, prospective, multiple-dose, open-label pharmacokinetic study, lidocaine patches were applied to healthy men and women for three consecutive days. Ten subjects received four lidocaine patches every 24 hours (group 1), and 10 subjects received four patches every 12 hours (group 2). Serial samples of venous blood were obtained to determine pharmacokinetic data. Overall tolerability and safety were assessed, and skin sensory testing was conducted to determine whether local anesthetic activity was produced.
The mean maximum plasma lidocaine concentrations at steady state with lidocaine patches applied in groups 1 and 2 were 186 and 225 ng/mL, respectively, compared with the reported mean maximum plasma concentration of 130 ng/mL with the labeled dosage (12 hr/day). The area under the concentration time curve for one dosage interval at steady state was 3550 and 4506 ng·hr/mL for groups 1 and 2, respectively. No loss in sensation at the application site was reported. No patient had edema, and most cases of erythema were very slight. No systemic adverse events were judged to be related to the patches.
Continuous application for 72 hours of four lidocaine patches 5%, changed every 12 or 24 hours, produced plasma lidocaine concentrations that remained well below those that typically produce antiarrhythmic effects or toxicity. Mild application-site erythema occurred in most patients, but no systemic adverse reactions were judged to be related to the patches. No loss in sensation at the application site was reported.
The lidocaine patch 5% (Lidoderm, Endo Pharmaceuticals, Chadds Ford, PA) is a targeted peripheral analgesic designed to treat peripheral neuropathic pain with minimal risk of systemic adverse effects. The patch facilitates lidocaine diffusion across the skin, where the drug binds to sodium channels that are present in abnormally high numbers on hyperactive or damaged nociceptors. When bound to these sodium channels, lidocaine reduces the abnormal ectopic discharges produced by damaged and dysfunctional peripheral nerves and interrupts conduction of the pain signal, thus alleviating pain. This system prevents lidocaine from entering the plasma in any clinically meaningful concentrations.
The lidocaine patch 5% is labeled for the treatment of the severe neuropathic pain of postherpetic neuralgia (PHN). PHN is the most frequently encountered neurologic disorder associated with herpes zoster (shingles). A chronic neuropathic pain disorder, PHN is characterized by burning or paroxysmal pain, exquisite skin sensitivity, abnormal pain perception, sensory loss, allodynia, and hyperalgesia and can significantly compromise a patient's quality of life. Recent studies have confirmed the safety and efficacy of the lidocaine patch for the relief of PHN with the maximum labeled dosage of three patches applied to the painful, intact skin for 12 hours per day (12 hours on and 12 hours off per 24-hour period), as well as extended application of up to four patches for 18 hours per day.
Because of the refractory nature of neuropathic pain and its substantial impact on the quality of life, it is not surprising that patients with a good response to the lidocaine patch are reluctant to remove the patch after 12 hours, fearing that the pain will return. Further, the success of this treatment modality in PHN has led clinicians to explore its utility in other pain states (e.g., complex regional pain syndrome, postmastectomy pain, postthoracotomy pain, a variety of peripheral neuropathies, myofascial pain, low-back pain, and osteoarthritis). Optimal dosage for these conditions may require more than three patches to cover the most painful area and application for longer than 12 hours per day. This study, in which four lidocaine patches were applied for 24-hour periods (both once daily and every 12 hours) on three consecutive days, was designed to assess the safety, tolerability, and pharmacokinetics of continuous (24 hours per day) application of the lidocaine patch. In addition, skin sensory testing was performed under the patch to reconfirm that the lidocaine patch does not produce an anesthetic effect.
