O

C 2H 5

HO

12

C 2H 5

O
H

HO

17

13

CH3

16
9

14

10

11

HO

5
4

(1)

15

(2)

Cl
HO

HO

O
O

HO

CH3
Cl
O

CH3
CH3
O

(3)

O
Cl

HO

(4)

C 2H 5

CH3
F
O

(5)

Potency: 1 < 3 < 4 <2 < 5

3 main features:
1. 9-halogen
2. 16,17-substitution
3. 21-halogen/hydroxyl/ester

Clindamycin salts
clindamycin phosphate vs clindamycin hydrochloride

pseudomembranous colitis topical clindamycin

HCl clindamycin PO4
clindamycin clindamycin HCl
0.025% tretinoin 5
clindamycin PO4

Q15: Clindamycin salts

Clindamycin lincosamides macrolides

Clindamycin HCl
Description

Hydrated HCl salt

Clindamycin PO4
Hydrated phosphate ester

pH in water

4.4

3.5-4.5

pKa

7.6

0.964, 6.081

Partition coefficient

185

0.03

References: from Dalacin-C and Dalacin-T monographs

3

Clindamycin salts

Clindamycin HCl salt conjugate acid of a weak base pKa = 7.6

pH 5.4 ionised P
= 185 unionised
systemic side effects

Clindamycin PO4 ester water soluble ester

hydrolysed clindamycin base pKa = 1.0 6.1
ionised clindamycin HCl
clindamycin anaerobes clindamycin PO4
phosphatase
anaerobes

* vehicles topical
clindamycin
References:
1. Krautheim, A and Gollnick H. Transdermal penetration of topical drugs used in the treatment of
acne. Clinical Pharmacokinetics, 42 (2003) 1287-1304.
2. http://www.pharmacy.wsu.edu/courses/PharS531/Stability%20I.2.htm
3. Dalacin-C and Dalacin-T Monographs

Adapalene
Adapalene vs Tretinoic acid
Adapalene first synthetic retinoid 3rd generation
retinoids naphthoic acid adamantane ring

THF

Adapalene-advantages
Topical retinoid tretinoin (all-trans-retinoic acid)

1. Adapalene aromatic polyene tretinoin

aliphatic polyene aromaticity adapalene
resonance effect tretinoin

Resonance effect
(for benzene ring)
7

Adapalene-advantages
2. Adapalene benzoyl peroxide (BPO) benzoyl radical
phenyl radical aromatic ring aliphatic
unsaturated bonds tretinoin
adapalene
BPO

Adapalene-advantages
3. Adapalene adapalene
aromatic carboxylic acid aliphatic carboxylic acid
tretinoin adapalene
retinoic acid receptor
receptor
tretinoin

Adapalene-mechanism of action
1. keratinocyte differentiation comedone formation
- adapalene 9-cis-RA RARs
RXRs ( ) RAR/ tretinoin
RARs adapalene

keratinocytes

Polyene linkage
(conjugated)
Carboxylic end

Cyclic end

10

Adapalene-mechanism of action
2. neutrophil chemotaxis lipoxygenase
neutrophil tretinoin

References:
1. Irby, CE et.al. A review of adapalene in the treatment of acne vulgaris. Journal of Adolescent Health,
43 (2008) 421-424.
2. Zaenglein, AL. Topical retinoids in the treatment of acne vulgaris. Seminars in Cutaneous Medicine
and Surgery, 27 (2008) 177-182.
11
3. http://pslc.ws/macrogcss/radical.html