PMID- 11354390
OWN - NLM
STAT- MEDLINE
DCOM- 20010906
LR  - 20211203
IS  - 0149-2918 (Print)
IS  - 0149-2918 (Linking)
VI  - 23
IP  - 4
DP  - 2001 Apr
TI  - Pharmacokinetics and tolerability of extended-release clarithromycin.
PG  - 566-77
AB  - BACKGROUND: Clarithromycin is a semisynthetic macrolide that exhibits 
      broad-spectrum activity against gram-positive, gram-negative, and atypical 
      respiratory tract and skin/skin structure pathogens, Mycobacterium species, and 
      Helicobacter pylori. It is indicated for the treatment of a wide variety of 
      respiratory and dermatologic infections in children and adults as well as 
      prophylaxis and treatment of Mycobacterium avium complex infection and peptic 
      ulcers due to H. pylori. OBJECTIVE: In this article, we review the results of 3 
      studies of the steady-state pharmacokinetic profiles of clarithromycin and 
      14(R)-hydroxy-clarithromycin after multiple oral once-daily doses of 500-mg 
      extended-release (ER) clarithromycin tablets. We also review the drug 
      tolerability in 2 phase III comparative clinical trials of immediate-release (IR) 
      and ER clarithromycin conducted in adults with acute maxillary sinusitis (AMS) 
      and acute exacerbation of chronic bronchitis (AECB). METHODS: In the 3 
      pharmacokinetic studies, multiple-dose regimens of clarithromycin IR (one 250-mg 
      or 500-mg tablet twice daily) and clarithromycin ER (one or two 500-mg tablets 
      once daily), administered to healthy male and female volunteers, were evaluated. 
      The effect of administration in nonfasting versus fasting conditions was assessed 
      as well. Tolerability information was collected from each adult patient enrolled 
      in phase III efficacy studies conducted to support the application for US Food 
      and Drug Administration approval for the treatment of AMS and AECB. Regimens 
      evaluated were 500 mg IR clarithromycin tablets twice daily or 1000 mg (2 x 500 
      mg) ER clarithromycin tablets once daily for 7 days (AECB) or 14 days (AMS). 
      RESULTS: Bioavailability of the ER clarithromyin tablet administered with food 
      was equivalent to that of the reference IR tablet, based on area under the plasma 
      concentration-time curve (AUC) for both parent compound and active metabolite. 
      The bioavailability of the ER tablet was 30% lower (based on clarithromycin AUC) 
      when administered under fasting versus nonfasting conditions. Compared with the 
      IR tablet, administration of the ER tablet resulted in significantly lower (P < 
      0.05) clarithromycin peak plasma concentration (Cmax), delayed time to Cmax, and 
      lower degree of concentration fluctuation, confirming its in vivo 
      extended-release characteristics. The most frequently reported adverse events 
      (AEs) in the phase III clinical trials were diarrhea, abnormal taste, and nausea 
      and were generally mild or moderate. The incidence of AEs was comparable for the 
      2 formulations. The severity of gastrointestinal AEs was significantly less for 
      the ER formulation than for the IR formulation (P = 0.018), as was the frequency 
      of premature study discontinuation due to gastrointestinal AEs or abnormal taste 
      (P = 0.004). CONCLUSIONS: The results from the 3 pharmacokinetic studies reviewed 
      demonstrate the bioequivalence of the ER and IR formulations and support the use 
      of this clarithromycin ER formulation in a once-daily dosing regimen in phase III 
      clinical trials. The ER tablet should be taken with food to maximize 
      bioavailability. The results of 2 phase III comparative clinical efficacy and 
      safety trials of clarithromycin ER tablets versus IR tablets in AMS and AECB 
      confirm the good tolerability of the ER formulation.
FAU - Guay, D R
AU  - Guay DR
AD  - Institute for the Study of Geriatric Pharmacotherapy, College of Pharmacy, 
      University of Minnesota, Minneapolis 55455, USA. guayx100@tc.umn.edu
FAU - Gustavson, L E
AU  - Gustavson LE
FAU - Devcich, K J
AU  - Devcich KJ
FAU - Zhang, J
AU  - Zhang J
FAU - Cao, G
AU  - Cao G
FAU - Olson, C A
AU  - Olson CA
LA  - eng
PT  - Clinical Trial
PT  - Clinical Trial, Phase III
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Clin Ther
JT  - Clinical therapeutics
JID - 7706726
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Delayed-Action Preparations)
RN  - H1250JIK0A (Clarithromycin)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Anti-Bacterial Agents/administration & dosage/*pharmacokinetics/*therapeutic use
MH  - Body Weight
MH  - Bronchitis/drug therapy
MH  - Clarithromycin/administration & dosage/*pharmacokinetics/*therapeutic use
MH  - Delayed-Action Preparations
MH  - Female
MH  - Humans
MH  - Male
MH  - Maxillary Sinusitis/drug therapy
MH  - Middle Aged
MH  - Racial Groups
EDAT- 2001/05/17 10:00
MHDA- 2001/09/08 10:01
CRDT- 2001/05/17 10:00
PHST- 2001/05/17 10:00 [pubmed]
PHST- 2001/09/08 10:01 [medline]
PHST- 2001/05/17 10:00 [entrez]
AID - S0149291801800606 [pii]
AID - 10.1016/s0149-2918(01)80060-6 [doi]
PST - ppublish
SO  - Clin Ther. 2001 Apr;23(4):566-77. doi: 10.1016/s0149-2918(01)80060-6.