PMID- 1462247
OWN - NLM
STAT- MEDLINE
DCOM- 19930112
LR  - 20131121
IS  - 0040-3709 (Print)
IS  - 0040-3709 (Linking)
VI  - 46
IP  - 5
DP  - 1992 Nov
TI  - Embryotoxicity studies of norfloxacin in cynomolgus monkeys. II. Role of 
      progesterone.
PG  - 429-38
AB  - Norfloxacin, an orally active fluoroquinolone antimicrobial, has been reported to 
      be embryolethal but not teratogenic when administered to pregnant cynomolgus 
      macaques prior to gestational day (GD) 36 at doses > or = 200 mg/kg/day. 
      Additional studies have been performed in an effort to examine the mechanism 
      responsible for this effect, particularly regarding the role of progesterone (P). 
      The first study (Study I) investigated the effect of norfloxacin administration 
      during early pregnancy (200 mg/kg/day; daily GD 20-30) in the absence of a 
      functional corpus luteum (CL). The CL was surgically removed from 16 gravid 
      females on GD 19 in order to focus on placental-derived P; ten were dosed with 
      norfloxacin and six received vehicle only. Embryolethality was observed for 7/10 
      (70%) of the treated animals during GD 25-31 versus 0/6 (0%) for controls. A 
      reduction in serum P was noted prior to embryonic loss, although no significant 
      effects on chorionic gonadotropin (CG), 17 beta-estradiol (E2), or P or E urinary 
      metabolites were observed. A second study (Study II) was performed in order to 
      evaluate the capacity of norfloxacin (200 mg/kg) to reduce CL-derived P in both 
      normally cycling and CG-stimulated nonpregnant females (ten treated, ten 
      controls; daily for 8 days). No effects on P production or on luteal phase or 
      menstrual cycle lengths were observed. The third study (Study III) was designed 
      to examine the effect of norfloxacin on the metabolism and excretion of P in 
      nonpregnant females. Silastic P implants were placed subcutaneously in order to 
      maintain constant P levels during a 10 day treatment regimen (200 mg/kg/day; ten 
      controls, nine treated). Five of the controls and four of the norfloxacin-treated 
      females also received 14C-P intravenously within 1 hr of the last dose of 
      norfloxacin in order to study excretory patterns. No significant differences 
      between control and treated groups were observed. The results of these studies 
      combined suggest that the developmental toxic effects observed in prior studies 
      and Study I are specific to pregnancy and directly related to placental-derived P 
      production.
FAU - Cukierski, M A
AU  - Cukierski MA
AD  - California Primate Research Center, University of California, Davis 95617.
FAU - Hendrickx, A G
AU  - Hendrickx AG
FAU - Prahalada, S
AU  - Prahalada S
FAU - Tarantal, A F
AU  - Tarantal AF
FAU - Hess, D L
AU  - Hess DL
FAU - Lasley, B L
AU  - Lasley BL
FAU - Peter, C P
AU  - Peter CP
FAU - Tarara, R
AU  - Tarara R
FAU - Robertson, R T
AU  - Robertson RT
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Teratology
JT  - Teratology
JID - 0153257
RN  - 0 (Chorionic Gonadotropin)
RN  - 4G7DS2Q64Y (Progesterone)
RN  - 4TI98Z838E (Estradiol)
RN  - N0F8P22L1P (Norfloxacin)
SB  - IM
MH  - Animals
MH  - Chorionic Gonadotropin/metabolism
MH  - Corpus Luteum/drug effects/metabolism
MH  - Estradiol/metabolism
MH  - Female
MH  - Fetal Death/*chemically induced/metabolism
MH  - Gestational Age
MH  - Macaca fascicularis
MH  - Norfloxacin/*toxicity
MH  - Pregnancy
MH  - Progesterone/*metabolism
EDAT- 1992/11/01 00:00
MHDA- 1992/11/01 00:01
CRDT- 1992/11/01 00:00
PHST- 1992/11/01 00:00 [pubmed]
PHST- 1992/11/01 00:01 [medline]
PHST- 1992/11/01 00:00 [entrez]
AID - 10.1002/tera.1420460507 [doi]
PST - ppublish
SO  - Teratology. 1992 Nov;46(5):429-38. doi: 10.1002/tera.1420460507.