PMID- 2718139
OWN - NLM
STAT- MEDLINE
DCOM- 19890619
LR  - 20131121
IS  - 0040-3709 (Print)
IS  - 0040-3709 (Linking)
VI  - 39
IP  - 1
DP  - 1989 Jan
TI  - Embryotoxicity studies of norfloxacin in cynomolgus monkeys: I. Teratology 
      studies and norfloxacin plasma concentration in pregnant and nonpregnant monkeys.
PG  - 39-52
AB  - Norfloxacin, a new orally active antibiotic, was investigated in cynomolgus 
      monkeys for potential developmental toxicity. Fifty-seven monkeys were 
      administered a control vehicle or norfloxacin by nasogastric gavage during the 
      major period of organogenesis on gestational days (GD) 21 through 50 at doses of 
      0, 50, 100, 150, or 200/300 mg/kg/day. There was no evidence of teratogenicity at 
      any dose level. Maternotoxicity and a significant increase in embryolethality 
      occurred following doses of 200/300 mg/kg/day. The maternotoxicity was not 
      expected based on range-finding studies in nonpregnant female monkeys, which 
      showed no signs of toxicity in doses up to 500 mg/kg/day. Additional studies were 
      conducted to determine if norfloxacin caused similar toxicity later in gestation. 
      Forty-six pregnant monkeys were dosed with a control vehicle or 200 mg/kg/day 
      norfloxacin for one of three 10-day periods on GD 36-45, 71-80, or 111-120. There 
      were no maternotoxic, embryotoxic, or fetotoxic effects observed. Plasma 
      concentrations of norfloxacin in five cynomolgus monkeys following 50 and 200 
      mg/kg oral doses were not dose-proportionate. However, at a given dose, 
      administered in cross-over fashion, plasma concentrations of norfloxacin were 
      higher in nonpregnant females (approximately 20-40%) than during pregnancy when 
      the same subject was compared. At the no-observed-effect dose for maternal and 
      embryotoxicity (50 mg/kg), peak plasma concentrations of norfloxacin in pregnant 
      cynomolgus monkeys are approximately threefold higher than those observed in 
      human volunteers receiving norfloxacin at the maximum recommended therapeutic 
      dose of 400 mg (5.7 mg/kg based on 70 kg body weight) twice per day.
FAU - Cukierski, M A
AU  - Cukierski MA
AD  - California Primate Research Center, Davis.
FAU - Prahalada, S
AU  - Prahalada S
FAU - Zacchei, A G
AU  - Zacchei AG
FAU - Peter, C P
AU  - Peter CP
FAU - Rodgers, J D
AU  - Rodgers JD
FAU - Hess, D L
AU  - Hess DL
FAU - Cukierski, M J
AU  - Cukierski MJ
FAU - Tarantal, A F
AU  - Tarantal AF
FAU - Nyland, T
AU  - Nyland T
FAU - Robertson, R T
AU  - Robertson RT
AU  - et al.
LA  - eng
GR  - RR00169/RR/NCRR NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Teratology
JT  - Teratology
JID - 0153257
RN  - 0 (Teratogens)
RN  - N0F8P22L1P (Norfloxacin)
SB  - IM
MH  - Animals
MH  - Body Weight/drug effects
MH  - Embryonic and Fetal Development/drug effects
MH  - Female
MH  - Macaca fascicularis
MH  - Maternal-Fetal Exchange
MH  - Norfloxacin/blood/*toxicity
MH  - Organ Size/drug effects
MH  - Pregnancy
MH  - Pregnancy, Animal/blood/*drug effects
MH  - *Teratogens
EDAT- 1989/01/01 00:00
MHDA- 1989/01/01 00:01
CRDT- 1989/01/01 00:00
PHST- 1989/01/01 00:00 [pubmed]
PHST- 1989/01/01 00:01 [medline]
PHST- 1989/01/01 00:00 [entrez]
AID - 10.1002/tera.1420390106 [doi]
PST - ppublish
SO  - Teratology. 1989 Jan;39(1):39-52. doi: 10.1002/tera.1420390106.