1.

Acyclovir topical
a. Acyclovir Pharmacokinetics – Absorption – Bioavailability
Not appreciably absorbed into systemic circulation following topical application to intact
skin. Not detected in blood or urine of immunocompromised adults following application of 5%
ointment to intact skin (4.5 inch2) at a dosage of 25 mg (1-cm ribbon) 4 times daily for 7 days.
Following topical application of 5% ointment in patients with localized varicella-zoster virus
(VZV) infections, plasma acyclovir concentrations were ≤0.28 mcg/mL or ≤0.78 mcg/mL in
those with normal or impaired renal function, respectively. Following repeated (5 times daily for
4 days) topical application of 5% cream to intact skin (710 cm2) in adult males, plasma acyclovir
concentrations measured 1 hour after the final application were undetectable or just above the
limits of detection. Systemic absorption of 5% cream not evaluated in children <18 years of age
(Pharmacists, 2007)

b. Lack of biovailability
ACV is effective against cutaneous infections due to HSV‑1, whose target site is the
basal epidermis. However, it has been suggested that ACV topical therapy has a low efficacy,
due to the lack of penetration of a sufficient amount of the drug to the target site. In this way,
Zanowiak and Jacobs found a good relationship between the free drug concentration at the basal
epidermis and the in vivo antiviral efficacy for a variety of ACV topical formulations. The
development of an effective ACV topical preparation prompted researchers to try several
approaches. In some studies superior antiviral activity was demonstrated using different vehicles,
percutaneous absorption enhancers and iontophoresis. Another possible strategy to achieve site
specific drug delivery would be the use of particulate drug carriers (microparticles and
nanoparticles). These carriers possess certain advantages for topical application, since sustained
release is important to supply the skin with the drug over a prolonged period of time. The
objective of this work was to obtain a high concentration of ACV in the basal epidermis, where
viral lesions are usually located, with the use of ACV-loaded solid lipid nanoparticles (ACV-
SLNs).
SLNs have been utilized to enhance the skin/dermal uptake of several pharmacological
agents such as triptolide, isotretinoin, podophyllotoxin, and prednicarbate, demonstrating the
potential of SLNs to be employed as the carrier for the topical delivery of penciclovir.
 (Gide et al., 2013)

c. Nanoemulsion
Topical and Transdermal Applications
Skin lesion and blisters due to infection of HSV can be treated with the application of
acyclovir in the form of topical ointment or transdermal cream. Topical and transdermal
formulations act as vehicles for antiviral agents besides rendering protective layer to prevent
further virus entry and spread from a particular site of infection. These formulations also
improve the healing time of cold sores and blisters as the application is localised at the site of
infection. However, acyclovir ointment has been reported to have only moderate efficacy
depending on the severity of the infection and the clinical condition of patients. Moreover,
frequent applications of acyclovir topical cream are required to attain its therapeutic effect. Also,
it has been reported that acyclovir cream and ointment have difficulties in penetrating the
epidermal layer of the skin. Due to slow absorption of the drug at the site of application, research
into new and improved formulations for acyclovir topical ointment has received significant
attention.
Additionally, nanoemulsion and to an extent microemulsion-based topical formulations
have been developed for treatment of cutaneous herpes infection. The applications of these
acyclovir formulations exhibited good skin permeation profile and resulted in HSV-1
suppression at the site of infection. A study on the effect of microemulsion-based topical
formulations of acyclovir for the treatment of cutaneous herpetic infections showed a positive
improvement where no herpetic skin lesion was observed after one week of treatment.
(Hassan et al., 2016)
2. Terapi PHN
a. Terapi Topikal
1) Patch lidokain 5%
2) Patch capcaisin

b. Terapi Oral
1) Gabapentin : dapat diberikan 3x100 mg/hari atau diberikan 300 mg single dose
2) Pregabalin : dapat diberikan 2-3x100-150 mg/hari
3) Tricyclic Antidepressan : 10-25 mg single dose
4) Opioid Analgesik : morfin 5-15 mg/4 jam
(Schmader & Dworkin, 2018)

Bibliography
Gide, P.S., Gidwani, S.K. & Kothule, K.U., 2013. Enhancement of transdermal penetration and
bioavailability of poorly soluble acyclovir using solid lipid nanoparticles incorporated in
gel cream. Indian J Pharm Sci, 75(2), pp.138-42.

Hassan, H. et al., 2016. Antiviral Nanodelivery Systems: Current Trends in Acyclovir

Administration. Hindawi, 1(1), pp.1-8.

Pharmacists, A.S.o.H.-S., 2007. Acyclovir topical. [Online] (1) Available at:

https://www.drugs.com/monograph/acyclovir-topical.html [Accessed 16 Januari 2019].

Schmader, K. & Dworkin, R., 2018. Herpes Zoster and Postherpetic Neuralgia. In Essentials of
Pain Medicine. 2nd ed. New York. pp.233-40.